Inclusion Criteria:

1. Histologically confirmed carcinoma of a primary tumor site and stage indicated in Table 3 of the protocol. 2. Tumor with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. 3. HLA-A*02:01 allele determined by testing performed in a CLIA certified laboratory. Participants may be enrolled based on low resolution typing (i.e., HLA-A*02) but the HLA-A*02:01 allele type must be confirmed prior to apheresis. 4. Measurable disease per RECIST Criteria Version 1.1 or PERCIST. 5. Age > 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. 7. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy tests is not required for women who have had a bilateral oophorectomy or hysterectomy. 8. Men and women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control; abstinence; tubal ligation or vasectomy) prior to study entry and for four months after treatment. Should a women become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. 9. Seronegative for HIV antibody, hepatitis B surface antigen (sAg), and hepatitis C antibody. If a hepatitis C antibody test is positive, then testing for antigen by reverse transcription polymerase chain reaction (RT-PCR) must be negative. 10. Participants must have organ and marrow function as defined below: 1. Leukocytes > 3,000/Mantle cell lymphoma (mcL) 2. Absolute neutrophil count > 1,500/mcL 3. Platelets > 100,000/mcL 4. Hemoglobin > 9.0 g/dL 5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL. 6. Serum aspartate aminotransferase (AST) (SGOT)/ alanine transaminase (ALT)(SGPT) < 2.5 x upper limit of normal (ULN) 7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). 8. international normalized ratio (INR) or activated partial thromboplastin time ( aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or aPTT within therapeutic range and no history of severe hemorrhage. 11. Participants must be able to understand and be willing to sign the written informed consent document. 12. Participants must agree to participate in protocol CINJ 192103 (Pro2021002307) for gene therapy long term follow up and in protocol Cancer Institute of New Jersey (CINJ) 192002 (Pro2021000281) for biospecimen collection study.Note: Patients may have undergone minor surgical procedures with the past three weeks, aslong as all toxicities have recovered to Grade 1 or less.

Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from

participation in this study: 1. Prior systemic therapy or definitive chemoradiation for the cancer that is being treated on this protocol. 2. Current treatment with another investigational agent. 3. History of severe allergic reactions to compounds of similar chemical or biological composition to agents used in this study. 4. Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements. 5. Subjects with HLA-A*02:01 damaging mutation or allele loss or other molecular resistance detected by research or clinical sequencing will not be eligible. 6. Documented LVEF of less than or equal to 45% tested. The following participants will undergo cardiac evaluations: 1. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or 2. Age > 50 years old 7. Participants with baseline screening pulse oxygen level of <92% on room air will not be eligible. If the underlying cause of hypoxia improves, they may be reevaluated. 8. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells. These potential risks may also apply to other agents used in this study. 9. Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the treatment. 10. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications). 11. Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible. 12. Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to: 1. Carcinoma in situ 2. Cutaneous skin cancers requiring only local excision 3. Low grade non-muscle invasive bladder cancer 4. Low grade prostate cancer 13. Subjects who received a live vaccine within 30 days prior to enrollment are not eligible. 14. Determination by the Principal Investigator that participation is not in the best interest of the research subject or may jeopardize the safety of the subject or integrity of the clinical trial data.

Key Inclusion Criteria

Patient has ECOG performance status of 0-1One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor perlocal assessmentOther potentially oncogenic PIK3CA mutations may be considered but must be approved bythe Sponsor prior to enrollment.Part 1 [Escalation] - Ability to provide archived tumor tissue or be willing to undergopretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 [Expansion] -Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutationretrospectively.Key Inclusion for RLY-2608 Single Agent Arm
• [For Part 1: Escalation]: Evaluable disease per RECIST v1.1
• [For Part 2: Expansion]: Measurable disease per RECIST v1.1
• Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy.
• Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor
• Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types:Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian,head and neck squamous cell, and cervical cancers Group 5: unresectable or metastaticsolid tumors with PIK3CA double mutations In addition, the SRC (with Sponsor approval)may choose to open additional group(s) of 20 participants to study the clinical activity,safety, and PK/PD with other specified solid tumor types.Key Inclusion for Combination Arms:
• Doublet combination arms [Part 1 and Part 2]: Evaluable disease per RECIST v1.1
• Triplet combination arms:
• [Part 1 and Part 2 Dose Expansion, Group 1]: Evaluable disease per RECIST.
• [Part 2 Dose Expansion, Group 2]: Measurable disease per RECIST. Bone-only lytic or lytic/blastic disease with at least 1 measurable soft-tissue component per RECIST may be eligible.
• [For Part 1 and Part 2]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy and must have initiated treatment with a gonadotropin-releasing hormone (GnRH) agonist at least 4 weeks prior to start of study drug with continuation of GnRH agonist for the duration of study treatment (GnRH agonist recommended for males).
• Had previous treatment for breast cancer with: [Does not apply to triplet combination arms, Part 2 Dose Expansion, Group 2]: 1. ≤1 line of chemotherapy in the metastatic setting 2. ≥1 CDK4/6 inhibitor in either the adjuvant and/or metastatic setting 3. ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and 4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment[For double combination arm; Part 2 Dose Expansion, Group 2]: Received prior treatmentwith a PI3Kα, AKT, or mTOR inhibitor and discontinued the inhibitor due to intoleranceand not disease progression, where intolerance is defined as treatment discontinuationdue to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other thansevere hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxisand Stevens-Johnson syndrome.[For triple combination arms; Part 1 dose escalation]: Participants who had previoustreatment for breast cancer with PI3Kα, AKT, mTOR inhibitors and discontiuned due toparticipant/physician decision, intolerance, or disease progression will be considered.[For triple combination arms, Part 2 Dose Expansion, Group 2]: Participants must beintolerant to or have declined standard therapy for locally advanced or metastaticHR+/HER2- PIK3CA-mutated breast cancer. Prior endocrine therapy and CDK4/6inhibitors areallowed as follows: 1. Participants must have progressed during (neo)adjuvant endocrine therapy or within12 months of completing (neo)adjuvant endocrine therapy with an AI or tamoxifen. 2. If a CDK4/6 inhibitor was included as part of (neo)adjuvant therapy, disease must have recurred/progressed >12 months after completion of the CDK4/6 inhibitor portion of (neo)adjuvant therapy

Key Exclusion Criteria

Prior treatment with: 1. PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation). 2. Immune checkpoint inhibitors. 3. Triplet combinations RLY-2608 + CDK4 or CDK4/6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only:i. Prior systemic chemotherapy or antibody drug conjugate for locally advanced ormetastatic disease. ii. Prior CDK2, CDK4, or CDK4/6 inhibitor as treatment for locallyadvanced or metastatic disease.iii. Prior treatment with fulvestrant or any selective ER degrader, with the exception ofpatients who have received fulvestrant or any selective ER degrader as part ofneoadjuvant therapy only and with treatment duration ≤6 months.Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasmaglucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.History of allergy or hypersensitivity to any components or excipients of PI3Kinhibitors. For combination arms only: allergy or hypersensitivity to any components orexcipients of fulvestrant, palbociclib, ribociclib, and/or PF-07220060 as appropriate forthe combination.Past medical history of or ongoing ILD, or pneumonitis requiring intervention.Participants with past history of resolved Grade 1 pneumonitis may be considered, exceptin triple combination arms.The following cardiac criteria:
• Mean resting corrected QT interval (QTc) >460 msec
• For triple combination arm with ribociclib: Mean QTcF ≥450 msec (this is what we confirmed is shown in the redacted version of the protocol.CNS metastases or primary CNS tumor that is associated with progressive neurologicsymptoms

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:
• Has histologically confirmed HER2+ locally advanced unresectable breast cancer or metastatic breast cancer
• Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load before allocation
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 7 days before start of study interventionArm 1:
• Has received at least a minimum of 2 and a maximum of 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
• Had disease progression on or after any previous trastuzumab deruxtecan (T-DXd) treatmentArm 2:
• Has received no more than 5 prior lines of anti-HER2 therapy in the locally advanced ormetastatic settingArm 3:
• Has received and had disease progression from T-DXd treatment in any setting and amaximum of 3 prior lines of anti-HER2 therapy in the locally advanced or metastaticsetting. T-DXd must be the most recent therapy received before enrollment.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:
• Uncontrolled or significant cardiovascular disease
• History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/interstitial lung disease
• Has clinically severe respiratory compromise
• Has any history of or evidence of any current leptomeningeal disease
• Has clinically significant corneal disease
• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection
• HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• Evidence of spinal cord compression or brain metastases
• Has an active infection requiring systemic therapy
• Concurrent active HBV and HCV infection
• Has had major surgical procedure (excluding placement of vascular access) less than 28 daysArm 3 ONLY
• Has received prior treatment with tucatinib, lapatinib, or neratinib, or anyinvestigational HER2-targeted tyrosine kinase inhibitors in the locally advanced ormetastatic setting

Inclusion Criteria:

1. Participant has signed the informed consent before all study specific activities are conducted. 2. Women or men aged ≥18 years (or the minimum age of consent in accordance with the local law), at the time of informed consent signature. Female participants may be of any menopausal status.
• Postmenopausal status is defined as follows or in accordance with local regulations: 1. Age ≥60 years or 2. Age <60 years and amenorrhea for 12 or more months (without an alternative cause) and follicle-stimulating hormone value and an estradiol level within the postmenopausal range per local laboratory reference or 3. Documentation of bilateral oophorectomy, at least 1 month before first dose of trial therapy.
• Premenopausal and perimenopausal women (who do not fit postmenopausal criteria) and men must be receiving a luteinizing hormone-releasing hormone (LHRH) agonist and must be initiated at least 3 weeks (4 depending on local label) before the start of trial therapy and are planning to continue LHRH agonist treatment during the study treatment. 3. Histopathological or cytological confirmed ER+, HER2-, breast cancer, per local laboratory, as per the American Society of Clinical Oncology/College of American Pathologists guidelines. Note: In the context of this trial, ER status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without progesterone positivity. 4. Documented radiological disease progression during or after the most recent therapy. 5. At least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Tumor lesions previously irradiated or subjected to any locoregional treatment will only be considered measurable if there is clear, documented progression at the treated site. For participants with bone only disease, lesions: must be lytic or mixed (lytic + blastic / sclerotic), confirmed and accurately assessed by computed tomography or magnetic resonance imaging, and must have an identifiable soft tissue component meeting the definition of measurability per RECIST v1.1. Note: participants with blastic / sclerotic bone lesions only are not eligible. 6. Eastern Cooperative Oncology Group performance status of 0 or 1. 7. Participant has adequate bone marrow and organ function, as defined by the following laboratory values: 1. Absolute neutrophil count ≥1.5 × 10^9/liter (L) 2. Platelets ≥100 × 10^9/L 3. Hemoglobin ≥9.0 grams/deciliter (g/dL) 4. Creatinine is ≤ 1.5 x upper limit of normal (ULN) or if creatinine is > 1.5 x ULN, then creatinine clearance must be ≥50 milliliters/minute based on the Cockcroft-Gault formula. Note: C-G formula:
• Creatinine clearance (male) = ([140-age in years] × weight in kilograms [kg])/ ([serum creatinine in milligrams/deciliter (mg/dL)] × 72)
• Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/ ([serum creatinine in mg/dL] × 72) f. Serum albumin ≥3.0 g/dL (≥30 g/L) g. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN. If the participant has liver metastases, ALT and AST ≤ 5 × ULN h. Total serum bilirubin <1.5 × ULN except for participants with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤ 1.5 × ULN.Additional Criteria for the Alpelisib Combination (Phase 1b and Arm A): In general, theprescription information of the respective combination drug should be consulted forinstructions/restrictions with respect to interactions with concomitant medications. 1. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation by local laboratory assessment. 2. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of which was in combination with a cyclin-dependent kinase targeting enzymes CDK4 and CDK6 (CDK4/6) inhibitor.Additional Criteria for the Everolimus Combination (Phase 1b and Arm B), the AbemaciclibCombination (Arm C), the Ribociclib Combination (Phase 1b and Arm C), and the PalbociclibCombination (Phase 1b): One or up to two prior hormonal therapies in the advanced ormetastatic setting, one of which was in combination with a CDK4/6 inhibitor.Additional Criteria for the Palbociclib Combination (Arm D), the Abemaciclib Combination(Arm D), and the Ribociclib Combination (Arm D): One or up to two prior hormonaltherapies in the advanced or metastatic setting.Additional Criteria for Capivasertib Combination (Phase 1b and Arm E): Recruitment inthis combination will occur only in countries where capivasertib is locally approved andavailable. 1. PIK3CA/AKT1/PTEN-alteration as detected by an FDA and/or locally approved test (local result). 2. One or up to two prior hormonal therapies in the advanced or metastatic setting or participants who have radiological evidence of breast cancer recurrence or progression within 12 months from the end of adjuvant treatment with endocrine therapy, as these participants are considered as first line relapsed participants. Prior CDK4/6i treatment is allowed but not required.

Exclusion Criteria:

1. Active or newly diagnosed central nervous system metastases, or meningeal carcinomatosis. Note: Participants with stable brain or subdural metastases are allowed if the participant has completed local therapy and was on a stable or decreasing dose of corticosteroids at baseline for management of brain metastasis for at least 4 weeks before starting treatment in this study. The dose must be ≤2.0 mg/day of dexamethasone or equivalent. Any signs (for example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment. 2. Participants with advanced, symptomatic visceral spread, who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement >50%. 3. Prior chemotherapy or elacestrant in the advanced/metastatic setting. 4. Participants with known germline BRCA mutation without prior treatment with a PARP inhibitor before study entry. 5. Prior therapy with elacestrant or other investigational selective estrogen receptor degraders, or investigational alike agents such as selective estrogen receptor modulators, selective estrogen receptor covalent antagonists, complete estrogen receptor antagonists, and proteolysis-targeting chimeras, in the metastatic setting. Prior treatment with fulvestrant is not exclusionary, except for Arm E, as it is an approved medication. 6. Participant has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, except basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative therapy. Other malignancies with low risk of recurrence may be considered eligible with Sponsor approval. 7. Uncontrolled significant active infections.
• Participants with hepatitis B virus and/or hepatitis C virus infection must have undetectable viral load during screening.
• Participants known to be human immunodeficiency virus+ are allowed if they have undetectable viral load at baseline. 8. Documented pneumonitis/interstitial lung disease prior to Cycle 1 Day 1. 9. Major surgery within 28 days before starting trial therapy. 10. Inability to take oral medications, refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the study drug. 11. Known intolerance to elacestrant or any of its excipients. 12. Pregnant and breast-feeding women are excluded from the study. In addition, women of childbearing potential are excluded who:
• Within 28 days before starting trial therapy, did not use a highly effective method of contraception.
• Do not agree to use a highly effective method of contraception (Appendix F) or abstain from heterosexual intercourse throughout the entire study period and for 120 days after trial therapy discontinuation. 13. Men or women who do not agree to abstain from donating sperm or ova, or to use a highly effective method of contraception, 28 days prior, during the course of the treatment period and for 120 days after the last dose of study treatment. 14. Participant is currently receiving or received any of the following medications prior to first dose of trial therapy: • Anti-cancer therapy within 14 days (28 days for anticancer antibody based treatment) or 5 half-lives, whichever is shorter. Please note: Toxicity from prior therapy must be resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 Grade ≤1, except alopecia and peripheral sensory neuropathy (Grade ≤2).
• Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 14 days or 5 half-lives, whichever is shorter, (refer to https://drug-interactions.medicine.iu.edu/maintable.aspx or https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug- interactions-table-substrates-inhibitors-and-inducers).
• Herbal preparations/medications within 7 days. These include, but are not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng.
• Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to starting trial therapy. 15. Evidence of ongoing alcohol or drug abuse as assessed by the investigator. 16. Any severe medical or psychiatric condition that, in the Investigator's opinion, would preclude the participant's participation in a clinical study.Additional Criteria for the Alpelisib Combination (Phase 1b and Arm A): 1. Prior therapy with alpelisib or any other phosphoinositide 3-kinase (PI3K) inhibitor. 2. Type 1 diabetes or uncontrolled type 2 diabetes (fasting plasma glucose level of >140 mg/dL [7.7 millimole (mmol)/L], or glycosylated hemoglobin [HbA1c] level of >6.4%). 3. Known intolerance to alpelisib or any of its excipients. 4. Participant is currently receiving or received drugs known to be a breast cancer resistant protein inhibitor (for example, curcumin, cyclosporine A, eltrombopag, febuxostat, fostamatinib, rolapitant, teriflunomide) within 14 days or 5 half-lives, whichever is shorter, prior to first dose of trial therapy (refer to Table 5.2 of https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-inter actions-table-substrates-inhibitors-and-inducers). 5. Participant has ongoing osteonecrosis of the jaw from previous or concurrent treatment with bisphosphonates or denosumabAdditional Criteria for the Everolimus Combination (Phase 1b and Arm B): 1. Prior therapy with everolimus. 2. Known intolerance to everolimus or any of its excipients.Additional Criteria for the Abemaciclib Combination (Arm C): 1. Prior therapy with abemaciclib in the advanced or metastatic setting. Adjuvant therapy with abemaciclib is also exclusionary. 2. Known intolerance to abemaciclib or any of its excipients. 3. History of deep vein thrombosis or pulmonary embolism (unless on anticoagulation), cerebrovascular accident, or myocardial infarction, in the past 6 months. Participants on anticoagulation should have been on a stable dose for at least 3 months prior to enrollment.Additional Criteria for the Ribociclib Combination (Phase 1b and Arm C): 1. Prior therapy with ribociclib in the advanced or metastatic setting. Prior adjuvant therapy with ribociclib is also exclusionary. 2. Known intolerance to ribociclib or any of its excipients. 3. QTcF interval corrected by Fridericia formula (QTcF) values ≥450 milliseconds (msec). 4. Participants who already have or who are at significant risk of developing QTc prolongation, including participants with:
• Long QT syndrome
• Uncontrolled or significant cardiac disease including recent (6 months) myocardial infarction, congestive heart failure, unstable angina, and brady-arrhythmias
• Electrolyte abnormalities (K+, Ca++, Phos, Mg++) ≥Grade 1 5. Participant is currently receiving or received drugs known to prolong QT interval within 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.Additional Criteria for the Palbociclib Combination (Phase 1b): 1. Prior therapy with palbociclib in the advanced or metastatic setting. 2. Known intolerance to palbociclib or any of its excipientsAdditional Criteria for the Palbociclib Combination (Arm D): 1. Prior therapy with a CDK4/6i in the metastatic setting. 2. Known intolerance to palbociclib or any of its excipients.Additional Criteria for the Abemaciclib Combination (Arm D): 1. Prior therapy with any CDK4/6i. 2. Known intolerance to abemaciclib or any of its excipients.Additional Criteria for Ribociclib Combination (Arm D): 1. Prior therapy with a CDK4/6i in the advanced or metastatic setting. 2. Known intolerance to ribociclib or any of its excipients. 3. QTcF values ≥450 msec. 4. Participants who already have or who are at significant risk of developing QTc prolongation, including participants with:
• Long QT syndrome
• Uncontrolled or significant cardiac disease including recent (6 months) myocardial infarction, congestive heart failure, unstable angina, and brady-arrhythmias
• Electrolyte abnormalities (K+, Ca++, Phos, Mg++) ≥Grade 1 5. Participant is currently receiving or received drugs known to prolong QT interval within 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.Additional Criteria for Capivasertib Combination (Phase 1b and Arm E): Recruitment inthis combination will occur only in countries where capivasertib is locally approved andavailable. 1. Prior treatment with any of the following: AKT, PI3K and mammalian target of rapamycin inhibitors and, for Arm E, fulvestrant. 2. Known intolerance to capivasertib or any of its excipients. 3. QTcF values ≥470 msec or factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval. 4. Clinically significant abnormalities of glucose metabolism as defined by any of the following: Participants with diabetes mellitus type 1; participants with diabetes mellitus type 2 requiring insulin treatment or participants with HbA1c level of >8.0% (63.9 mmol/mol).

Inclusion Criteria:

1. Aged ≥18 years at Screening 2. Diagnosis of histologically confirmed breast cancer that is unresectable. The following subsets of breast cancer are included: 1. Patients with triple-negative breast cancer, advanced or metastatic 2. Patients with hormone receptor (HR) positive, ER positive, HER2 negative advanced or metastatic breast cancer 3. Has measurable disease in accordance with RECIST 1.1 obtained by imaging within 28 days prior to C1D1 4. Other therapies are not indicated (eg, resistant or intolerant to taxanes and/or an anthracycline-containing regimen) for treatment of advanced or metastatic breast cancer 5. Has a life expectance of at least 24 weeks 6. Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 at screening 7. Has adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before C1D1 (Note: labs will also be repeated pre-dose on C1D1 to confirm eligibility): a. Hemoglobin ≥9 g/dL (≥90 g/L) b. Adequate renal function by estimated glomerular filtration rate (eGFR) defined as a creatinine clearance >50 mL/min (>0.84 mL/s) (Cockcroft-Gault equation) and normalized to body surface area c. Peripheral absolute neutrophil count (ANC) of ≥1.5×109/L d. Platelet count of ≥100×109/L without growth factor/transfusion e. Total bilirubin <1.5× upper limit of normal (ULN); or ≤3×ULN if the patient has Gilbert's disease f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5×ULN, with liver metastasis <5×ULN g. International normalized ratio (INR) <1.5 and prothrombin time (PT) ≤1.5×ULN, unless both of the following conditions are met: i. Patient is receiving anticoagulant therapy, and ii. PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulant h. Activated partial thromboplastin time (aPTT) ≤1.5×ULN, unless both of the following conditions are met: i. Patient is receiving anticoagulant therapy, and ii. PT or PTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

1. Received any line of treatment for advanced or metastatic breast cancer within 21 days or 5 half-lives (whichever is longer) prior to randomization 2. Currently receiving any hormone replacement therapy, unless discontinued within 21 days prior to randomization 3. Received IV 5-FU or oral 5-FU analog in the 4 weeks prior to C1D1 4. Received DPD inhibitor within 4 weeks prior to C1D1 5. Has homozygous or compound heterozygous DPYD variants that result in complete or near-complete absence of DPD activity 6. Cardiac: 1. Has history or presence of clinically significant abnormal 12-lead electrocardiogram (ECG) results, in the Medical Monitor or Investigator's opinion 2. Has prolonged QTc (with Fridericia's correction) of >480 msec performed at Screening 3. Has a history of prolonged QTc interval, ventricular tachycardia/fibrillation or significant ventricular arrhythmia, or Torsades de Pointes, or a history of ventricular ablation for arrhythmia 4. Has congenital long QT syndrome or a family history of long QT syndrome 5. Has other clinically significant cardiac disease including, but not limited to, myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery ≤12 months prior to randomization, congestive heart failure
• Class II per the New York Heart Association, or history of myocarditis 7. Is pregnant or breastfeeding

Inclusion Criteria:

• Patient has ECOG performance status of 0-1
• One or more known primary oncogenic PIK3CA mutation(s)
• Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 4 weeks prior to randomization and must be willing to continue on it for the duration of the study.
• Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent
• Measurable disease per RECIST v1.1 or evaluable bone-only disease.
• Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with: 1. At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting 2. 1 prior line of CDK4/6 inhibitor therapy in one of the following settings: 1. CDK4/6 inhibitor + ET in the ABC setting 2. CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET 3. Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had >1 prior line of CDK4/6 inhibitor and are not eligible

Exclusion Criteria:

• Prior treatment with any of the following: 1. CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases 2. PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway 3. Immunotherapy 4. Antibody drug conjugates
• Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL, or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
• Clinically significant, uncontrolled cardiovascular disease
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
• Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients
• Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K

Participants are eligible to be included in the study only if all of the followingcriteria apply: 1. Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent. 2. Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines as evaluated by a central laboratory 3. Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment. 4. Has measurable disease per RECIST version 1.1. 5. Is eligible to receive one of the chemotherapy options listed in the physician's choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine). 6. Participants with history of treated or clinically inactive CNS metastases are eligible as specified in the protocol. 7. Has a life expectancy of at least 6 months, in the opinion of the investigator. 8. Has adequate hematologic parameters as defined in the protocol. 9. Has adequate hepatic function as specified in the protocol. 10. Has creatinine clearance ≥ 30 mL/minute as calculated per local institutional guidelines. 11. Has LVEF ≥ 50% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention. 12. Has ECOG performance status of 0 or 1. 13. Participant agrees to the following based on sex assigned at birth. 1. Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 5 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice, whichever is longer:

• Refrain from donating fresh unwashed semen.
• Use contraception as follows as specified in the protocol 2. Female participants:
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
• Is a women of nonchildbearing potential OR
• Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency during the study intervention period and for at least 5 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance/standard practice, whichever is longer.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 3 days before the first dose of study intervention.
• Additional requirements for pregnancy testing during and after study intervention are provided in the protocol.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 14. Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol.Participants are excluded from the study if any of the following criteria apply:Medical Conditions 1. Has known or suspected leptomeningeal disease. 2. Has uncontrolled or significant cardiovascular disease. 3. Has toxicity related to prior cancer therapy that has not resolved to ≤ Grade 1, with exceptions as stated in the protocol. 4. Has uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. 5. Has known HIV infection. 6. Has active hepatitis B or C infection. 7. Has an active SARS-CoV-2 infection. Participants with prior infection that has resolved per local institutions' requirements and screening guidance are eligible. 8. Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab. 9. Is unable to receive trastuzumab treatment due to medical contraindications. 10. Has any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site. 11. Has any condition that would prevent treatment with the physician's choice of chemotherapy. 12. Has any issue or condition that in the opinion of the investigator would contraindicate the participant's participation in the study or confound the results of the study. Prior/Concomitant Therapy 13. Has a history of prior allogeneic bone marrow, stem cell, or solid organ transplantation. 14. Was treated with any local or systemic antineoplastic therapy (including hormonal therapies for breast cancer) or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization. 15. Has a history of trauma or major surgery within 4 weeks prior to randomization. Other Exclusions 16. Has a known hypersensitivity to any components of the study drugs, including chemotherapy. 17. Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.

1. Inclusion Criteria: Subjects must meet all the following criteria to participate in

this study. 1. Signed, written informed consent obtained prior to any study procedures. 2. Age > 18 years at the time of informed consent. 3. Metastatic solid tumor with ≥ 10% of tumor cells positive for KK-LC-1 by IHC assay. Due to the low frequency of KK-LC-1 expression in most cancers, screening will focus on gastric, NSCLC, TNBC, and cervix cancers. The IHC test will be performed by the Rutgers Cancer Institute, Department of Biorepository Services. 4. HLA-A*01:01 allele by HLA haplotype test. 5. Measurable disease per RECIST Criteria Version 1.1 at time of enrollment. 6. Prior treatment with cancer type-specific standard of care systemic cancer therapy is required. Standard treatment options must be considered and declined. Documentation of rationale is required if a subject is deemed unsuitable for standard therapy. 7. Subjects with < 3 brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Patients with surgically resected brain metastases are eligible. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. 9. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy tests is not required for women who have had a bilateral oophorectomy or hysterectomy. 10. Women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control; abstinence; tubal ligation or vasectomy) prior to study entry and for 12 months after treatment. Should a women become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. 11. Participants must have organ and marrow function as defined below: 1. Leukocytes > 3,000/mcL 2. Absolute neutrophil count > 1,500/mcL 3. Platelets > 100,000/mcL 4. Hemoglobin > 9.0 g/dL 5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL. 6. Serum AST (SGOT)/ALT (SGPT) < 2.5 x ULN 7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). 8. INR or a PTT ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or PTT within therapeutic range and no history of severe hemorrhage. 12. Serology:
• HIV antibody negative
• Hepatitis B antigen negative
• Hepatitis C antibody negative or HCV RNC negative (i.e., no current HCV infection) 13. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the KK-LC-1 TCR T cells. Adverse events from prior therapy must have resolved to ≤ grade 1 according to CTCAE Version 5.0 or have demonstrated clinical stability and meet the eligibility criteria for the protocol. 14. Oxygen saturation ≥ 92% on room air. 15. Left ventricular ejection fraction ≥45% by echocardiogram or MUGA for patients 50 years of age or older.

Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from

participation in this study: 1. Current treatment with another investigational agent. 2. History of severe allergic reactions to compounds of similar chemical or biologic composition to agents in used in study. 3. Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements. 4. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with KK-LC-1 TCR T cells, breastfeeding should be discontinued if the mother is treated with KK-LC-1 TCR cells. The potential risks may also apply to other agents used in this study. 5. Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the treatment. 6. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications). 7. Subjects with HLA-A*01:01 damaging mutation or allele loss or other molecular resistance detected by clinical or research genomic profiling will not be eligible. 8. Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible. 9. Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to: 1. Carcinoma in situ 2. Cutaneous skin cancers requiring only local excision 3. Low grade non-muscle invasive bladder cancer 4. Low grade prostate cancer Participants with prior or concurrent malignancy that do not meet the above criteria are excluded. 10. Subjects who received a live vaccine within 30 days prior to enrollment are not eligible. 11. Determination by the Principal Investigator that participation is not in the best interest of the research subject or may jeopardize the safety of the subject or integrity of the clinical trial data.

Inclusion Criteria:

• Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic.
• Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
• Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine therapy (ET) in the locally advanced or metastatic setting.
• Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy ≥ 6 months

Exclusion Criteria:

• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines.
• Have received more than one-line of therapy for locally advanced or metastatic disease.
• Have received prior chemotherapy for metastatic breast cancer
• Treatment with anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half -lives, whichever is shorter, prior to initiation of study drug. Treatment with an approved oral endocrine therapy (ET) within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug.
• Poor peripheral venous access
• Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption
• History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.

Eligibility Criteria to Collect Optional Correlative Blood and Tissue at Local Recurrence

• Written informed consent (stage I) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Male or female age ≥ 18 years at the time of consent.
• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample. If there is insufficient tissue from the most recently collected sample, earlier tissue may be used on a case-by-case basis if permission is granted by the sponsor investigator.
• Patient has locoregional recurrence of breast cancer: locoregional recurrence is defined as invasive recurrence in the ipsilateral breast, axilla, regional nodes, or chest wall.

  Inclusion Criteria for Treatment Phase:

  Subject must meet all of the following applicable inclusion criteria to participate inthis study:
  • Written informed consent (stage II/ main consent) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific screening procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Male or female age ≥ 18 years at the time of consent. NOTE: Both pre- and post-menopausal women are eligible. Post-menopausal status is defined as:
  • Prior bilateral oophorectomy
  • Age ≥60
  • Age <60 and amenorrhea for the last 12 or more months(in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range.
  • ECOG Performance Status of 0-1 within 28 days prior to registration.
  • If patient is receiving tamoxifen or toremifene, a washout period of 5 half-lives (i.e. 35 days) prior to registration is required (during that period the participant can take AI).
  • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
  • Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample. If there is insufficient tissue from the most recently collected sample, earlier tissue may be used on a case-by-case basis if permission is granted by the sponsor investigator.
  • Patients have had adequate local treatment for locoregional recurrence (LRR) of breast cancer.
  • Locoregional recurrence is defined as recurrence in the ipsilateral breast, axilla, regional lymph nodes, or chest wall.
  • Local treatment is defined as either surgery, radiation therapy, or a combination of both if indicated.
  • Adequate local therapy is surgery with negative microscopic margins. Radiation therapy is mandated for patients with microscopically involved margins and recommended for all patients who had not received radiotherapy as part of their primary treatment.
  • Patients who have distant metastatic disease will not be eligible.
  • Prior treatment with neoadjuvant and adjuvant chemotherapy and ET is allowed.
  • Patients must enroll within 6 months of the last local treatment, either local surgery or radiation; or systemic chemotherapy (if patient is receiving chemotherapy), whichever occurred last. Chemotherapy after local therapy is allowed. ET for recurrent disease is allowed for up to 12 months prior to enrollment.
  • Patient has no contraindication to the adjuvant ET in the trial and is planned to be treated or continue treatment with ET.
  • Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
  • Hematological
  • Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L
  • Platelets: ≥ 100 x 109/L
  • Hemoglobin (Hgb): ≥ 9.0 g/dL
  • Renal
  • --Estimated glomerular filtration rate (eGFR): ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula
  • Hepatic
  • Bilirubin: ≤ upper limit of normal (ULN) except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN
  • Aspartate aminotransferase (AST): ≤ 2.5 × ULN except for patients with liver metastasis, who are only included if the AST is < 5 × ULN
  • Alanine aminotransferase (ALT): ≤ 2.5 × ULN except for patients with liver metastasis, who are only included if the ALT is < 5 × ULN
  • Coagulation
  • --International Normalized Ratio (INR) : ≤ 1.5 × ULN (unless is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug)
  • Electrolytes ---Potassium, Magnesium, and Total Calcium (corrected for serum albumin): Within normal limits or corrected to within normal limits with supplements.
  • Standard 12-lead ECG values defined as
  • QTcF interval at screening < 450 msec (QT interval using Fridericia's correction)
  • Resting heart rate 50-90 bpm (determined from the ECG)
  • Females of childbearing potential who are sexually active with a male able to father a child must have a negative pregnancy test (serum or urine) within 14 days prior to registration and must be willing to use a highly effective method of contraception that does not contain estrogen and/or progesterone. See the protocol for definition of childbearing potential.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
  • Ability to swallow and retain oral medication.

  Exclusion Criteria for Treatment Phase:

  Subjects meeting any of the criteria below may not participate in the study:
  • Patient with a known hypersensitivity to any of the excipients of ribociclib.
  • Patient who has received prior CDK4/6 inhibitor for recurrent disease. Patients who received a CDK4/6 inhibitor in the adjuvant setting may participate if they have been off therapy for at least 1 year prior to diagnosis of recurrent disease.
  • Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
  • Pregnant or breastfeeding or planning to become pregnant during the trial (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
  • Patients with distant metastases of breast cancer beyond regional lymph nodes as defined by AJCC (8th edition).
  • Treatment with any investigational drug within 30 days prior to registration or participation in any other type of medical research judged not to be scientifically or medically compatible with this study. Enrollment or planned enrollment in another study that does not involve an investigational drug will be allowed at the discretion of the treating investigator.
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g., chronic pancreatitis, chronic active hepatitis, HIV, active untreated or uncontrolled fungal, bacterial or viral infections, etc.). Testing to be done at investigator's discretion.
  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
  • History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
  • Documented cardiomyopathy
  • History of Left Ventricular Ejection Fraction (LVEF) < 50%
  • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
  • Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
  • Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug)
  • Inability to determine the QTcF interval
  • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
  • Systolic Blood Pressure (SBP) >160 or <90 mmHg
  • Patient is currently receiving any of the following substances and cannot be discontinued 7 days prior to Cycle 1 Day 1:
  • Concomitant medications, herbal supplements, and/or fruits (e.g., grapefruit, pummelos, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of CYP3A4/5,
  • Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
  • Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: a short duration (<5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
  • Patient with an uncontrolled psychiatric condition that, in the investigator's judgment, may cause unacceptable safety risks, impede research integrity and compliance, or interfere with the objectives of the study.

Inclusion Criteria:

• Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
• Male or female, aged ≥18 years at the time of giving informed consent.
• Are willing and able to comply with scheduled visits, the treatment schedule, the planned study assessments (including participant completed diaries) and other requirements of the study. This includes that they are able to understand and follow study-related instructions.
• Have confirmed locally recurrent inoperable or mTNBC as defined by the most recent American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines. Note, participants initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer must have histological confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis site.
• Systemic treatment naïve locally advanced/metastatic participants are eligible if:
• They have received no prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, immunotherapy, or investigational agents.
• They have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months has elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, or date of last radiation therapy, whichever occurred last) and first documented local or distant disease recurrence. This also includes participants initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer prior to TNBC diagnosis.
• Participants who received one prior systemic therapy in the locally advanced/metastatic setting are eligible if:
• They have received one systemic chemotherapy in the metastatic setting and have progressed on first line therapy. Radiographic progression must have been documented. Radiographic progression is defined as unequivocal progression of existing tumor lesions or developing new tumor lesions as assessed by the investigator.
• They have had a recurrence-free interval of ≥6 months if they have received treatment with curative intent in the past. A recurrence-free interval of ≥6 months is required for all participants (both first- and second-line treatment settings) who have received prior treatment for breast cancer with curative intent.
• Have provided a tissue sample, archival or fresh, during the screening period (bone biopsies, fine needle aspiration biopsies, and samples from pleural or peritoneal fluid are not acceptable; participants with only one target lesion are not eligible to provide a biopsy). If an archival tumor sample is not available, the participant must undergo a fresh biopsy, if medically feasible to be eligible for the study.
• Have at least one measurable lesion as the targeted lesion based on RECIST version 1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Have a minimum life expectancy of >3 months.
• Have adequate organ function, as defined below:
• Hematology:
• Absolute neutrophil count ≥1.5 × 10^9/L (without G-CSF support within two weeks prior to Cycle 1, Day 1).
• Platelet count ≥100 × 10^9/L (without transfusion within 2 weeks prior to Cycle 1, Day 1).
• Hemoglobin ≥90 g/L or 5.6 mmol/L. Note: Criterion must be met without packed red blood cell transfusion or without erythropoietin dependency within the prior 2 weeks before receiving the first dose of study treatment.
• Liver function:
• Total bilirubin ≤1.5 × upper limit of normal (ULN).
• With Gilbert's syndrome total bilirubin <3 mg/dL and direct bilirubin ≤ULN. Note, Gilbert's syndrome must be documented appropriately as past medical history.
• Participants without liver metastasis alanine aminotransferase and aspartate aminotransferase ≤2 × ULN.
• Participants with liver metastasis alanine aminotransferase and aspartate aminotransferase ≤5 × ULN.
• Albumin ≥3.0 g/dL.
• Renal function: Creatinine clearance ≥50 mL/min. Cockcroft-Gault formula. Note, in participants who will be treated with gemcitabine plus carboplatin, creatinine clearance should be ≥60 mL/min.
• Qualitative urine protein ≤1+. If qualitative urine protein ≥2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein result is <1 g, the participant can be enrolled.
• Coagulation function: International normalized ratio or prothrombin time and activated partial thromboplastin time ≤1.5 × ULN unless the participant is receiving anticoagulation therapy as long as prothrombin or activated partial thromboplastin is within therapeutic range of intended use of anticoagulant.
• Are women of childbearing potential (WOCBP) who have a negative serum beta human chorionic gonadotropin pregnancy test. Women who are postmenopausal (defined as 12 months with no menses without an alternative medical cause) or permanently sterilized (verified by medical records) will not be considered WOCBP and therefore will not be required to undergo pregnancy testing.
• Are WOCBP who agree to practice a highly effective form of contraception and to require the use of barrier contraception methods, starting at at the time of giving informed consent and continuously until 6 months after receiving the last study treatment.
• Are men who are sterile or if they are potentially fertile (i.e., are not surgically [e.g., have had a vasectomy] or congenitally sterile) and sexually active with a partner of childbearing potential, who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the study, starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of IMP.
• Agree not to donate germ (ova, oocytes, sperm) for the purposes of assisted reproduction during study, starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of IMP.

Exclusion Criteria:

• Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the study or within 6 months after the last dose of IMP.
• Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the study, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol described requirements.
• Have received any of the following therapies or drugs prior to the initiation of study:
• Participants who received prior treatment with a PD(L)-1/Vascular Endothelial Growth Factor bispecific antibody.
• Have received a systemic anticancer regimen within 4 weeks prior to the initiation of study treatment or have received palliative radiotherapy within 7 days prior to the initiation of study treatment, or have received any other chemotherapy, curative/palliative radiotherapy, biologic therapy (including tumor vaccines, cytokines, or growth factors for tumor control) or any experimental antitumor drugs within 4 weeks prior to the initiation of study treatment.
• Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-alpha [IFN-α], interleukin-2 [IL-2], or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: Excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
• Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.
• Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of study treatment.
• Received broad-spectrum IV antibiotics therapy within 3 weeks prior to initiation of study treatment.
• Use of any non-study investigational medicinal product within five half-lives of first dose or within 4 weeks, whichever is longer, before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
• Have undergone major organ surgery (core needle biopsies are allowed >7 days prior study start), significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of study treatment or plan to undergo elective surgery during the study. Placement of vascular infusion devices is allowed.
• Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Have spinal cord compression or central nervous system metastases that is untreated and symptomatic or requires treatment with corticosteroids or anticonvulsants for associated-symptom control. Exception: Treated brain metastases which is no longer symptomatic and for which no corticosteroid or anticonvulsant treatment is needed (the participant must be recovered from the acute toxic effect of radiotherapy; study treatment assignment must be ≥2 weeks after completion of radiotherapy).
• Have active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Those who had a history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for those with clinically stable autoimmune thyroid disease or type 1 diabetes.
• Have had other malignant tumors within 2 years prior to the study treatment are not allowed. Except for those: who have been cured with local treatment (such as basal cell or squamous cell carcinoma of the skin, superficial or non-invasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary carcinoma of thyroid; including prostate cancer with CR within the past 3 years).
• Have any of the following heart conditions within 6 months prior to the study treatment:
• Acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, or other Grade 3 and above cardiovascular and cerebrovascular events.
• New York Heart Association functional classification ≥II heart failure or left ventricular ejection fraction <50%.
• Those who have ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, or congenital long QT syndrome. Participants with treated cardiac arrythmia/atrial fibrillation are allowed.
• Mean QT interval corrected by Fridericia's method (QTcF) >480 ms (the ECG can be repeated at the discretion of the investigator).
• Use of cardiac pacemaker.
• Cardiac troponin I or T >2 x ULN.
• Have any of the following hypertension or diabetic conditions prior to initiation of study treatment:
• Poorly controlled diabetes (fasting blood glucose ≥13.3 mmol/L [240 mg/dL] or HbA1C [≥8.5%]).
• Uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90 mmHg) while on antihypertensive medicine.
• A history of hypertensive crisis or hypertensive encephalopathy.
• Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra abdominal abscess for which an interval of 6 months must pass before the Screening Visit. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
• Participants with evidence of major coagulation disorders or other significant risks of hemorrhage such as:
• History of intracranial hemorrhage or intraspinal hemorrhage.
• Tumor lesions invading large blood vessels and are at significant risk of bleeding.
• Had clinically significant hemoptysis or tumor hemorrhage of any cause within 1 month prior to the initiation of study treatment.
• Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX) are allowed.
• Have uncontrolled tumor-related pain requiring analgesic treatment not managed by a stable analgesic regimen. For asymptomatic metastatic lesion, if its growth may cause dysfunction or intractable pain (e.g., current epidural metastasis unrelated to spinal cord compression), local treatment should be considered before screening, if appropriate.
• Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
• Have a known human immunodeficiency virus infection or known acquired immunodeficiency syndrome, with the following exceptions:
• Participants with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts ≥350 cells/µL per local laboratory should generally be eligible for the study.
• Participants who have not had an opportunistic infection within the past 12 months.
• Have a known history/positive serology for hepatitis B requiring active antiviral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Individuals with positive serology must have hepatitis B virus viral load below the limit of quantification.
• Have active hepatitis C virus infection; individuals who have completed curative antiviral treatment with hepatitis C virus viral load below the limit of quantification are allowed.
• Are subject to exclusion periods from another investigational study.
• Are vulnerable individuals, i.e., are individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. This includes all sponsor, study site, or third party (e.g., CRO, vendor) personnel directly involved in the conduct of the study and their family members or dependents, as well as all study site personnel otherwise supervised by the investigator.
• Participants with AEs from prior antitumor therapy that have not returned to Grade 1 (graded by NCI CTCAE version 5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, Grade 2 peripheral neuropathy or stable hypothyroidism under hormone replacement therapy) are not eligible for the study.
• Have superior vena cava syndrome or symptoms of spinal cord compression.
• Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease. Those with a history of pulmonary fibrosis, or currently diagnosed with severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function. Exception: Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
• Have active tuberculosis or history of tuberculosis that was not successfully treated.
• Have underlying condition(s) that may increase risk of the combination treatment or complicate the interpretation of toxicities and AEs, as judged by the investigator, or other scenarios that the investigators consider the participant is not eligible for the study.

Inclusion Criteria:

• A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
• The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• Female patients must be greater than or equal to 18 years of age.
• Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
• Age 50 years or under with spontaneous menses within 12 months; or
• Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
• Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
• Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
• The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
• Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• Patients may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
• For patients who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS (ductal carcinoma in situ) with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS (lobular carcinoma in situ) are eligible without additional resection.)
• For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
• Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
• By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
• By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
• Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
• Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
• Oncotype DX RS (recurrence score) requirements*:
• If node-negative:
• Oncotype DX RS must be RS 21-25, or
• Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as: low histologic grade with primary tumor size greater than 3 cm, intermediate histologic grade with primary tumor size greater than 2 cm, or high histologic grade with primary tumor size greater than 1 cm.
• If 1-3 nodes involved:
• Oncotype DX RS must be less than 26. * Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes the activity of certain genes in early-stage breast cancer) result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
• The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results. Patients with greater than or equal to 1% ER and/or PgR staining by IHC will be classified as positive.
• The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines based on local testing results.
• The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
• Short course of endocrine therapy of less than 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
• Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. This would include prior cancers treated with curative intent.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Radiation therapy should be used according to standard guidelines; the intended radiation therapy should be declared prior to pre-entry.

Exclusion Criteria:

• • Definitive clinical or radiologic evidence of metastatic disease.
• pT4 (pathological state) tumors, including inflammatory breast cancer.
• History of ipsilateral or contralateral invasive breast cancer. (Patients with synchronous and/or previous DCIS or LCIS are eligible.)
• If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation therapy), a mastectomy must have been performed for the current cancer.
• Life expectancy of less than 10 years due to co-morbid conditions in the opinion of the investigator.Known results from most recent lab studies obtained as part of routine care prior tostudy entry showing ANY of the following values:
• ANC (absolute neutrophil count) less than 1200/mm3;
• Platelet count less than 100,000/mm3;
• Hemoglobin less than 10 g/dL;
• Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than 1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin;
• AST(aspartate aminotransferase)(SGOT)/ALT (alanine transminase)(SGPT): greater than 3 × institutional ULN;
• Renal function of GFR (glomular filtration rate) less than 30 mL/min/1.73m2.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Any treatment with radiation therapy, chemotherapy, or biotherapy administered for the currently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen given for breast cancer prevention is allowed. Prior AI or GnRH for fertility preservation is allowed.
• Hormonally based contraceptive measures must be discontinued prior to pre-entry (including progestin/progesterone IUDs).
• Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible unless the HBV viral load is undetectable on suppressive therapy. Patients with a history of hepatitis C virus (HCV) infection are ineligible unless they have been treated and cured or have an undetectable HCV viral load if still on active therapy.
• Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to pre-entry.)
• Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.