Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol; 2. No gender limit; 3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib); 4. Expected survival time ≥3 months; 5. Histologically and/or cytologically confirmed locally advanced or metastatic solid tumors that are incurable or currently have no standard treatment; 6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years; 7. Must have at least one measurable lesion according to RECIST v1.1 definition; 8. ECOG 0 or 1; 9. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0; 10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%; 11. The level of organ function must meet the requirements on the premise that blood transfusion is not allowed within 14 days before the screening period and no cell growth factor drugs are allowed; 12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN; 13. The urine protein + 2 or 1000 mg / 24 h or less or less; 14. For premenopausal women with fertility may have to 7 days before beginning treatment for a pregnancy test, serum pregnancy must be negative, and must not be lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Anti-tumor therapy such as chemotherapy or biological therapy has been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil; 2. Prior receipt of an ADC drug with a TOPI inhibitor as a toxin; 3. History of severe heart disease or cerebrovascular disease; 4. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia; 5. Active autoimmune and inflammatory diseases; 6. Other malignant tumors diagnosed within 5 years before the first dose; 7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg); 8. A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis according to the RTOG/EORTC definition, or suspicion of such a condition during screening; 9. Complicated pulmonary diseases leading to clinically severe respiratory function impairment; 10. Patients with massive or symptomatic effusions or poorly controlled effusions; 11. Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large blood vessels; 12. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded; 13. Symptoms of active central nervous system metastasis; 14. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any excipients of BL-M14D1; 15. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 16. Anthracycline cumulative dose > 360 mg/m2 in previous (new) adjuvant therapy; 17. HIV antibody positive, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 18. Active infection requiring systemic therapy with serious infection within 4 weeks before informed consent; There were indications of pulmonary infection or active pulmonary inflammation within 2 weeks before informed consent; 19. Participated in another clinical trial within 4 weeks before the first dose; 20. Pregnant or lactating women; 21. A history of severe neurological or psychiatric illness; 22. Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent; 23. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent; 24. History of intestinal obstruction, inflammatory bowel disease, or extensive bowel resection or presence of Crohn's disease, ulcerative colitis, or chronic diarrhea; 25. Patients scheduled for vaccination or receiving live vaccine within 28 days before the first dose; 26. Other conditions for participation in the trial were not considered appropriate by the investigator.

Inclusion Criteria:

• Must be a candidate for standard of care (SOC) treatment of non small cell lung cancer (NSCLC) by concurrent platinum-based doublet chemotherapy with radiation therapy (cCRT) followed by consolidation durvalumab treatment as determined by the investigator and per local guidelines at screening
• Have a medical history of pathologically (histologically or cytologically) proven diagnosis of NSCLC within 3 months prior to enrollment/randomization
• Have locally advanced unresectable stage III NSCLC according to the eighth edition lung cancer stage classification
• Have at least 1 target lesion (primary lung lesion or involved lymph node[s]) per RECIST version 1.1 that is amenable to intratumoral and/or intranodal injection and intensity modulated radiation therapy (IMRT) as determined by the investigator at screening
• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Medical history of: (a) Primary immunodeficiency (b) Organ transplant that requires therapeutic immunosuppression
• Any of the following within 3 months prior to enrollment/randomization: severe or unstable angina, myocardial infarction, clinically significant ventricular arrhythmias or heart failure New York heart association functional classification class III to IV
• Another concurrent or prior primary malignancy within the last 36 months at informed consent
• Known allergies, hypersensitivity, or intolerance to any ingredients of JNJ-90301900 crystalline solution, platinum-based doublet chemotherapy (ChT), or durvalumab
• History of coagulation disorders, including: (a) Active bleeding diathesis or requirement for therapeutic anticoagulation or antiplatelet that cannot be interrupted or altered for JNJ-90301900 injection procedures, (b) Major thromboembolic events (for example, pulmonary embolism, cerebrovascular accident) within 3 months of enrollment or randomization

Inclusion Criteria:

• Patients must be < 50 years at the time of enrollment.
• Patients must have =< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being >= 3 mm and all of which must be =< 3 cm size.
• Note: Patient must have eligibility confirmed by rapid central imaging review.
• Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
• Patients must have a histological diagnosis of osteosarcoma.
• Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
• Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
• Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
• Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.

Exclusion Criteria:

• Patients with unresectable primary tumor.
• Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
• Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
• Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
• Patients with evidence of extrapulmonary metastatic disease.
• Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Inclusion criteria:

• Be more than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater)
• Have histologically or cytologically confirmed recurrent/metastatic (R/M) HNSCC that is considered incurable by local therapies: a. eligible primary tumor locations are the oral cavity, oropharynx, hypopharynx, or larynx; b. Must not have a primary tumor site of nasopharynx or primary tumor of unknown location; c. Must have documented local testing results per local regulations; d. Human papillomavirus (HPV) status must be known for participants with primary tumor location in oropharynx via p16 test, HPV DNA test, or high-risk HPV in situ hybridization (ISH). Any known p16, HPV DNA, or high-risk HPV ISH status of tumor must be negative
• Be treatment-naive for systemic therapy in the R/M setting
• Have an ECOG performance status of 0 or 1
• Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1Exclusion criteria:
• Have an uncontrolled illness
• Have untreated brain metastases or history of known presence of leptomeningeal disease
• Have a history of clinically significant cardiovascular disease
• Inadequate organ or bone marrow function
• Known allergies, hypersensitivity, contraindications, or intolerance to excipients of: Amivantamab, Pembrolizumab, Carboplatin, Cisplatin, 5-FU and Hyaluronidase

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 test is not required for women who have had a bilateral oophorectomy or hysterectomy. 10. 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 12 months after treatment. Should a woman 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 m² for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). 8. INR or aPTT ≤ 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 RNA 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. Participants must agree to participate in Rutgers protocol 192103 (Pro2021002307) for gene therapy long term follow up and in Rutgers protocol 192002 (Pro2021000281) or NIH protocol 16C0061 (Rutgers 192202) for biospecimen collection study.Note: Patients may have undergone minor surgical procedures within the past three weeks,as long 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. Current treatment with another investigational agent. 2. History of severe allergic reactions to compounds of similar chemical or biologic composition to agents used in study. 3. History of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test. 4. 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 greater than or equal to 50 years old 5. Participants with baseline screening pulse oxygen level of less than or equal to 92% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated. 6. 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. 7. 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. 8. 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. 9. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications). 10. 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. 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. Prior history of potentially severe autoimmune diseases without a current, active diagnosis is not exclusionary. 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 Participants with prior or concurrent malignancy that do not meet the above criteria are excluded. 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. 15. Hepatic metastases unless ≤ 5 lesions and no lesion ≥ 5 cm in greatest dimension. 16. Prior catheter related locoregional therapies to the liver: embolization (TAE), transarterial chemoembolization (TACE), transarterial radioembolization (TARE).

Inclusion Criteria:

• The participant (or legally acceptable representative if applicable) must provide written informed consent for the study. The participant may also provide consent for future unspecified research samples. However, the participant may participate in the study without participating in the future unspecified research sample collection. NOTE: Initial informed consent will remain valid throughout the 12-week period between surgical resection and study registration unless, in the opinion of the treating investigator, the participant experiences a significant change in medical or mental status.
• Males and females age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Patients must have undergone complete surgical resection of their stage I NSCLC between 4-12 weeks prior to registration and have negative surgical margins (R0).
• NOTE: Both squamous and non-squamous histologies are allowed into the study. Cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus "non-squamous histology".
• NOTE: Staging will be according to the AJCC 8th edition.
• Pathological tumor size must be 1.0 - 4.0 cm in greatest dimension. NOTE: According to AJCC 8th edition, subjects with lepidic predominant adenocarcinoma should be staged based on their invasive tumor size and not their total tumor size (i.e., subjects with lepidic predominant tumors whose invasive tumor size is less than 1 cm are not eligible, even if their total tumor size is 1.0 cm or greater).
• Surgery for this lung cancer must be completed at least 28 days prior to registration.
• Baseline CT chest must be performed within 28 days of randomization to ensure no evidence of disease.
• Must have either previous NGS and PD-L1 results available using the Dako 22C3 antibody or have archival tissue of surgical specimen from current diagnosis available to perform analyses. PD-L1 results via the Dako 22C3 antibody will be performed per standard of care from a CLIA-accredited laboratory and are required for stratification. If NGS results are not available, subjects must be able to provide at least 10 x 10µm unstained and 1 x 4µm H&E slides from current diagnosis for future NGS and/or other genetic analyses.
• Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. For subjects randomized to the pembrolizumab arm: If there is > 72 hours between the screening test and C1D1, another pregnancy test (urine or serum) must be performed and must be negative before the subject may start C1D1.
• NOTE: Females are considered of childbearing potential unless: they are postmenopausal; are surgically sterile; or they have a congenital or acquired condition that prevents childbearing. See Section 5.1.4 for definitions.
• NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who is using a highly effective contraceptive method (failure rate of <1% per year), or is abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) during the intervention period and for at least 120 days after the last dose of study drug. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study drug. See contraceptive guidance in Section 5.1.4 of the protocol.
• Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy after completion of study intervention.Hepatitis B screening tests are not required unless:
• Known history of HBV infection
• As mandated by local health authority
• Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.Hepatitis C screening tests are not required unless:
• Known history of HCV infection
• As mandated by local health authority
• HIV-infected participants are eligible but must have well-controlled HIV on anti-retroviral therapy (ART), defined as:
• Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at screening.
• Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.
• It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months before study entry (Day 1/randomization).
• Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1/randomization) and agree to continue ART throughout the study.
• Note: HIV screening testing is not required unless mandated by local health authority.
• 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

Exclusion Criteria:

• Current lung cancer is <1 cm or > 4 cm in size or is stage II, III, or IV.
• Patients with tumors that are known to harbor actionable EGFR mutations.
• Prior chemotherapy, radiation therapy, or immunotherapy for the treatment of this lung cancer.
• Has a known active additional malignancy that is progressing or has required active treatment within the past 2 years. NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
• Has had an allogenic tissue/solid organ transplant.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has active TB (Bacillus Tuberculosis) infection.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

Inclusion Criteria:

• Age ≥ 18 years old at the time of enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1
• Expected life expectancy ≥ 3 months
• Metastatic (Stage IV) NSCLC
• Histologically or cytologically confirmed squamous or non-squamous NSCLC
• Tumor demonstrates high PD-L1 expression ( TPS>50%) based on a 22C3 immunohistochemistry ( IHC) clinical assay approved / cleared by local health authorities.
• At least one measurable noncerebral lesion according to RECIST 1.1
• No prior systemic treatment for metastatic NSCLC.

Exclusion Criteria:

• Histologic or cytopathologic evidence of the presence of small cell lung carcinoma for which first-line approved therapies are indicated. For patients with non-squamous histology, actionable driver mutation testing results are required before randomization.
• Has received any prior therapy for NSCLC in the metastatic setting.
• Concurrent enrollment in another clinical study, unless patient is enrolled in a non-interventional clinical study or is completing survival follow -up.
• Known actionable genomic alterations for which first-line approved therapies are indicated
• Symptomatic CNS metastases, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease
• Other prior malignancy (including previously treated NSCLC) unless the patient has undergone curative therapy with no evidence of recurrence of the disease for 3 years prior to randomization
• Active autoimmune or lung disease requiring systemic therapy
• Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 5
• Severe infection within 4 weeks prior to randomization
• Major surgical procedures or serious trauma within 4 weeks prior to randomization
• History of noninfectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease

Inclusion Criteria:

• Participant has histologically confirmed locally advanced (unresectable) or metastatic non-small cell lung cancer (NSCLC) with documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutation result status, based on local or central testing.
• The participant's positive KRAS G12D mutation result (either in tumor tissue or plasma ctDNA) must be available prior to randomization.
• If the participant is enrolling based on a local testing result, the result may have been based on tissue or liquid (blood) testing. If the participant is enrolling via central testing, the eligibility sample must be from tissue.
• Participant must have progressed or experienced disease recurrence on or after platinum based chemotherapy (which includes but is not limited to platinum combinations with pemetrexed, paclitaxel, etoposide or gemcitabine) in combination with anti-PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially in the locally advanced (unresectable) or metastatic setting (participant who received anti PD-1/anti-PD-L1 antibody or platinum-based chemotherapy as first-line therapy in the locally advanced [unresectable] or metastatic setting may have received the combination of platinum-based chemotherapy and anti PD1/anti PD L1 antibody in the second line locally advanced [unresectable] or metastatic setting).
• No additional treatments are allowed in the locally advanced (unresectable) or metastatic setting, with the exception of: Anti-vascular endothelial growth factor (VEGF) therapy (e.g., bevacizumab), when administered in combination with platinum-based chemotherapy and/or anti-PD-1/PD-L1 as part of a standard regimen in the locally advanced (unresectable) or metastatic setting and
• Anti-CTLA-4 antibodies (e.g., ipilimumab, tremelimumab), when administered in combination with anti-PD-1/PD-L1 (with or without platinum-based chemotherapy) as part of a standard regimen in the locally advanced (unresectable) or metastatic setting.
• For the purposes of eligibility, for a participant who has received prior neoadjuvant or adjuvant therapy and has had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant therapy will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting (for those who received perioperative therapy, the entire course will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting).
• For the purposes of eligibility, for a participant with a history of unresectable Stage III disease who has received prior multi-modal therapy and has had recurrence on or within 6 months of completion of therapy, the multi-modal therapy will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting. If chemoradiation was followed by treatment with checkpoint inhibitor therapy (CPI) without documented progression between chemoradiation and CPI, the entire treatment course will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting, for the purposes of eligibility.
• Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate line of therapy.
• Female participant is not pregnant and at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP).
• WOCBP who has a negative urine or serum pregnancy test at screening (Specific to Japan: with a medical interview) and agrees to follow the contraceptive guidance from the time of informed consent through ≥ 6 months after the final setidegrasib administration or ≥ 2 months after the final docetaxel administration, as applicable.
• Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for ≥ 6 months after the final setidegrasib administration or ≥ 2 months after the final docetaxel administration, as applicable. (Note that this is stricter than some docetaxel product information/labeling documents due to the uncertainty regarding excretion of docetaxel in human milk.)
• Must not donate ova starting at first administration of study intervention and throughout the investigational period and for ≥ 6 months after the final setidegrasib administration or ≥ 2 months after the final docetaxel administration, as applicable.
• Participant consents to and provides a baseline tumor tissue and plasma specimen during prescreening and/or screening.
• Participant has an ECOG performance status of 0 or 1 within 7 days prior to randomization.

Exclusion Criteria:

• Participant has known untreated or symptomatic central nervous system (CNS) metastases. Participant with previously treated brain metastases may be eligible if they have stable CNS disease for ≥ 2 weeks prior to randomization, all neurologic symptoms have returned to baseline, there is no evidence of new or enlarging brain metastases on brain imaging performed within 28 days prior to randomization and they are receiving ≤ 10 mg/day of prednisone or equivalent. Participants with untreated CNS metastases, even if asymptomatic, are not eligible.
• Participant has mixed small-cell lung cancer and NSCLC histology.
• Participant has leptomeningeal disease as a manifestation of the current malignancy.
• Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
• Participant has known hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or anti HBV core antibody-positive) or known hepatitis C virus (HCV) (defined as HCV RNA [qualitative] detected) infection.
• Participant with human immunodeficiency virus (HIV) infection may be eligible if the participant has not had an opportunistic infection within the past 12 months. Participant must be on established antiretroviral therapy for ≥ 4 weeks, have a CD4+ T cell ≥ 200 cells/µL and must have an HIV viral load < 400 copies/mL prior to randomization (HIV testing is not required unless mandated by the local health authority).
• Participant has current grade ≥ 2 peripheral neuropathy.
• Participant has uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Participant with PleurX catheters in place may be considered for the study with medical monitor approval.
• Participant has received therapeutic or palliative radiation therapy within 14 days

prior to randomization (see first Exclusion Criteria for CNS metastases);

participant must have recovered from all radiotherapy related toxicity to ≤ grade 1, with the exception of alopecia (any grade of alopecia allowed).
• Participant has a known actionable mutation for which an approved targeted therapy is locally available, including, but not limited to, KRAS G12C mutation, EGFR mutation (exon 19 deletions, exon 21 L858R point mutation, T790M, exon 20 insertion), ALK or ROS1 rearrangement, NTRK fusion, NRG1 fusion, BRAF V600E mutation, MET exon 14 skipping mutation, RET rearrangement or HER2 activating mutation.
• Participant has received prior treatment with either docetaxel or a KRAS-targeting agent (including KRAS directed inhibitors, degraders, siRNA, vaccines and cellular therapies).
• Participant requires treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450 (CYP)3A or CYP2D6 or strong inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) or organic anion transporting polypeptide 1B3 (OATP1B3).

• Patients must have histologically or cytologically confirmed stage IV NSCLC (includes M1a, M1b, and M1c stage disease, AJCC 8th edition). Patients with Stage IIIB and IIIC disease are eligible if they are not candidates for combined chemotherapy and radiation; such cases should be discussed in a multidisciplinary tumor board.
• Eligible NSCLC tissue histologies will include squamous cell carcinoma (enrolled and treated in Arm 1), and nonsquamous histologies (e.g. adenocarcinoma, large cell carincoma, etc.; enrolled and treated in Arm 2). Patients with mixed squamous, e.g., adenosquamous, histology will be enrolled and treated on Study Arm 1. Patients with any evidence of Small Cell Carcinoma will be excluded from study participation.
• Patients may have ANY PD-L1 expression Tumor Proportion Score (TPS) status. Tissue testing for PD-L1 is strongly recommended. If PD-L1 expression TPS is unevaluable or the testing could not be completed, the patient may still be eligible.
• Patients must have measurable or non-measurable disease. The presence of malignant pleural fluid alone is sufficient to satisfy this eligibility criterion. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to study registration. NOTE: If patient receives pemetrexed, follow institutional guidelines to drain fluids.
• Patients must be ≥ 18 years of age.
• Patients must have an ECOG Performance Status of 0 to 2
• Patients must NOT have received the following:
• Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for metastatic lung cancer are ineligible. Chemotherapy and immunotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed between the last dose of the prior therapy and study registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 7 days has passed between

  completion of local therapy and study registration. Registration prior to

  treatment during the 7 days is allowed. Palliative radiation must be to non-target lesions.
  • Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
  • For Arm 1 (Squamous Lung Cancer): Patients must not have pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v.5.0. Patients must not have known sensitivity to any component of carboplatin or paclitaxel or nabpaclitaxel.
  • Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600), MET Exon14 skipping or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with asymptomatic new (at screening) or progressive brain metastases (active brain metastases at screening) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
  • Patients are eligible if off steroids for at least 7 days prior to protocol treatment.
  • Palliative radiation to non-target lesions (bone metastasis) is allowed if patient develops symptoms.
  • Anticonvulsants are allowed.
  • Patients with asymptomatic, sub-centimeter brain metastasis who at the discretion of investigators do not need immediate CNS directed therapies are eligible.
  • Patients with prior or concurrent 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.
  • Patients must not have known pre-existing and clinically active interstitial lung disease, or a known history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, etc.)
  • Patients must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment in the past 2 years (i.e. 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, etc.) is not considered a form of systemic treatment.
  • 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 II or better.
  • Patients must not have any other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug.
  • Patients must not receive any other investigational agents during the course of therapy.
  • Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from cytotoxic chemotherapy and the unknown risk of MK-3475 (pembrolizumab). Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until at least 120 days after the last dose of study treatment.All females of childbearing potential must have a blood test or urine study within 72hours prior to registration to rule out pregnancy.A female of childbearing potential is any woman, regardless of sexual orientation orwhether they have undergone tubal ligation, who meets the following criteria: 1) hasachieved menarche at some point; 2) has not undergone a hysterectomy or bilateraloophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancertherapy does not rule out childbearing potential) for at least 24 consecutive months(i.e., has had menses at any time in the preceding 24 consecutive months).
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or abstain from sexual intercourse from time of registration, while on study treatment, and continue for 120 days after the last dose of study treatment.
  • Patient must have the ability to understand and the willingness to sign a written informed consent document.
  • Patients must meet the following laboratory values within 14 days of randomization:
  • ANC ≥ 1500/mm3
  • Platelets ≥ 100,000/mm3
  • Hgb > 8 g/dL (Note: Patient may be transfused to meet this criteria)
  • PT/INR ≤ 1.5
  • Or if patient on therapeutic anticoagulation with Warfarin, PT/INR ≤ 3.0
  • Patients must have adequate liver function as determined by the following tests obtained within 14 days of randomization:
  • Total Bilirubin ≤ 1.5 mg/dL
  • SGOT (AST) < 5X upper limit of normal (ULN)
  • SGPT (ALT) < 5X upper limit of normal ULN)
  • Patients must have adequate renal function as determined by the following tests obtained within 14 days prior to randomization:Calculated creatinine clearance ≥ 45ml/min to be eligible to receive pemetrexed Serumcreatinine ≤ 1.5X institutional upper limit of normal (ULN)
  • Patients must not have a known history of active tuberculosis (TB).
  • Patients must not have a diagnosis of immunodeficiency or receive systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol treatment.
  • Patients must not have received a live vaccine within 30 days prior to randomization. Seasonal flu vaccines that do not contain live virus are permitted. COVID-19 vaccination per guidelines for cancer patients is permitted and encouraged.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.Head and Neck Cancer (Arm 3)
  • Patient must have histologically confirmed recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC) (excluding SCC of salivary glands, nasopharynx and skin) that is considered incurable by local therapies. The eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx. Unknown primary site will also be considered eligible.
  • Patients may have ANY PD-L1 expression Tumor Proportion Score (CPS) status. Tissue testing for PD-L1 IHC on samples demonstrating recurrent/metastatic disease is strongly recommended, though testing may be performed on initial diagnostic specimens. If PD-L1 expression CPS is unevaluable or the testing could not be completed, the patient will still be considered eligible.
  • Tumor expression of p16 by immunohistochemistry is highly desirable for patients with Oropharyngeal primaries. Positive p16 expression is defined as strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumor cells. If HPV status was previously tested using this method, no additional testing is required. If results are not available or are not possible patient will still be considered eligible.Note: Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testingby p16 IHC as by convention these tumor locations are assumed to be HPV negative.
  • Patients must have measurable or non-measureable disease. The presence of malignant pleural fluid or bone disease alone is sufficient to satisfy this eligibility criterion. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to study registration. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Patient must be ≥ 18 years of age.
  • Patient must have an ECOG performance status 0-2.
  • Patients must NOT have received the following:
  • Prior systemic chemotherapy or immunotherapy for recurrent/metastatic head and neck squamous cell carcinoma. Patients treated with any prior checkpoint inhibitors for recurrent/metastatic head and neck cancer are ineligible. NOTE: Patients who have received prior chemotherapy or cetuximab with radiation for curative intent treatment of locally advanced head and neck cancer whose disease has progressed after at least 6 months will be eligible.
  • Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
  • Patients who have endocrinopathies but are now stable on hormone supplementation and/or a daily prednisone dose of ≤ 10 mg (or equivalent doses of another glucocorticoid), will be permitted on this trial.
  • Patient must not have a severe infection within 4 weeks prior to randomization, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Patients must not have active tuberculosis.
  • Patient must not have a history of non-infectious pneumonitis requiring steroids at doses greater than or equal to 10 mg per day of prednisone or the equivalent on first line immunotherapy.
  • Patient must not have a history of solid organ transplantation or stem-cell transplant.
  • Patient must not be on immunosuppressive medication within 7 days prior to randomization except for: intranasal, inhaled, or topical steroids, local steroid injection, systemic corticosteroids at doses less than or equal to 10 mg per day of prednisone or the equivalent, or steroids used as premedication for hypersensitivity reactions.
  • Patient must not have an active autoimmune disease that requires systemic treatment within 2 years prior to randomization. Patients who are receiving replacement therapy for adrenal or pituitary insufficiency will not be excluded.
  • Patient must not have had a severe hypersensitivity reaction to any of the drug components used on this protocol or to chimeric or humanized antibodies or fusion proteins.
  • Patient must not have received any live vaccine within 30 days prior to randomization and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist® are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events).
  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.All patients of childbearing potential must have a blood test or urine study within 14days prior to randomization to rule out pregnancy.A patient of childbearing potential is defined as anyone, regardless of sexualorientation or whether they have undergone tubal ligation, who meets the followingcriteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy orbilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea followingcancer therapy does not rule out childbearing potential) for at least 24 consecutivemonths (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 120 days after last dose of study therapy.
  • Patient must have the ability to understand and the willingness to sign a written informed consent document.
  • Patient must have adequate organ and marrow function as defined below (these labs must be obtained ≤ 14 days prior to protocol randomization):
  • Absolute neutrophil count (ANC) ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hgb > 8 g/dL (Note: Patient may be transfused to meet this criteria)
  • Total bilirubin ≤1.5xULN OR Direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 × institutional ULN (< 5.0 x institutional ULN if hepatic metastases present)
  • Creatinine ≤ 1.5 x institutional ULN OR Measured or Calculated Creatinine Clearance ≥60 mL/min for subject with creatinine levels >1.5x institutional ULN
  • PT/INR ≤ 1.5
  • Or if patient on therapeutic anticoagulation with Warfarin, PT/INR ≤ 3.0
  • Patients with uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL) must have their calcium levels corrected prior to randomization.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients must not have untreated brain metastases or leptomeningeal disease.
  • Patients with a prior or concurrent 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.
  • Patient must not have significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to randomization, or unstable arrhythmia or unstable angina at the time of randomization.
  • Patient must not receive any other chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiation therapy, or experimental medications while on protocol treatment. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization and patients must be recovered from the effects of radiation (there is no required minimum recovery period).
  • Patient must not have any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the agents used in this protocol, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.

Inclusion Criteria:

• Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF); voluntarily participate in the study; be able to complete the study as per protocol requirements;
• Aged ≥ 18 years at the time of signing the ICF, male or female;
• Histologically or cytologically confirmed, locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC not suitable for radical treatment (complete surgical resection, concurrent/sequential radio-chemotherapy) according to the Union for International Cancer Control and the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition), and should meet the following criteria: 1. Subjects without actionable genomic alterations (AGAs):
• Subjects with non-squamous NSCLC must have documented negative test results for EGFR and ALK alterations. If no prior test results for EGFR and ALK are available, subjects must undergo EGFR and ALK testing at the study site. For subjects with squamous NSCLC, EGFR and/or ALK testing is not required prior to enrollment if their status is unknown;
• No other known actionable genomic alterations, such as ROS1, NTRK, BRAF, MET exon 14 skipping, and RET;
• Prior standard treatment failure of ≥ 1 line, including at least anti-PD-(L)1 antibody and platinum-based chemotherapy; 2. Subjects with AGAs:
• Previous test results confirming the presence of one or more actionable genomic alterations;
• Prior standard treatment failure of ≥ 1 line, including at least targeted therapy for driver gene alterations (patients with EGFR mutations must be previously treated with EGFR inhibitors) and platinum-based chemotherapy;
• At least one measurable lesion as per RECIST 1.1 within 4 weeks prior to randomization;
• Subjects who agree to provide archived tumor tissue specimens that meets the testing requirements (either from the most recent surgery or biopsy, preferably within 2 years) or agree to undergo a biopsy to collect tumor tissue for PD-L1 expression testing;
• The following conditions must be met in terms of the time of the first administration of the investigational product: at least 3 weeks (or 5 half-lives of the drug, whichever is shorter) from the previous major surgery, medical device treatment, locoregional radiotherapy (except for palliative radiotherapy for bone lesions), cytotoxic chemotherapy, immunotherapy, or biological product therapy; at least 2 weeks from the previous hormone therapy or small molecular targeted therapy; at least 1 week from the administration of the traditional Chinese medicine for anti-cancer indications or minor surgery; and recovery of treatment-induced AEs to Grade ≤ 1 (CTCAE v5.0, except for Grade 2 peripheral neurotoxicity and alopecia);
• ECOG PS score of 0-1 within 1 week prior to randomization;
• Life expectancy > 3 months;
• Adequate organ functions as confirmed by laboratory tests within 1 week prior to randomization (no blood transfusions or treatment with granulocyte colony-stimulating factor is allowed within 14 days prior to the first dose)
• Male and female subjects with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 6 months after the last dose of the investigational product; female subjects of childbearing age must be negative for pregnancy test within 7 days prior to enrollment.

Exclusion Criteria:

• Histologically or cytologically confirmed tumor containing components of small cell lung cancer, neuroendocrine carcinoma, or sarcomatoid carcinoma;
• Prior treatment with any medication targeting topoisomerase I, including chemotherapy or ADCs;
• Radical radiation therapy within 3 months prior to the first dose;
• History of any second malignancy within 2 years prior to randomization, except for early-stage malignancies (carcinoma in situ or stage I tumors) that have received radical treatment, such as non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma;
• History of adverse events leading to permanent discontinuation of immunotherapy, or occurrence of ≥ Grade 2 immune-related pneumonitis or myocarditis during prior immunotherapy;
• Presence of uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Presence of spinal cord compression or clinically active metastases to central nervous system (referring to untreated or symptomatic metastases, or metastases requiring corticosteroids or anticonvulsants to control associated symptoms), carcinomatous meningitis. Subjects who have previously received treatment for brain metastases (such as whole brain radiotherapy or stereotactic brain radiotherapy) may be eligible, provided that they are clinically stable for at least 4 weeks with no imaging evidence of brain metastasis progression;
• Subjects with current or prior history of clinically significant pulmonary impairment due to pulmonary comorbidities, including but not limited to any underlying lung disease (e.g., pulmonary embolism within 3 months prior to the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, interstitial pneumonia, pneumoconiosis, drug-related pneumonitis, and pleural effusion within 3 months prior to the first dose), any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), prior pneumonectomy that may interfere with the detection and management of suspected drug-related pulmonary toxicity, or history of with radiation pneumonitis within 6 months;
• Patients with any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except lacunar infarction, slight cerebral ischemia, or transient ischemic attack); (4) poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) (QTc intervals are calculated by Fridericia's formula); (5) poorly-controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg after active treatment);
• Patients with active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to randomization;
• Patients who have used moderate or potent CYP2D6 or CYP3A inhibitors or inducers within 2 weeks prior to randomization;
• Patients who have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 2 weeks prior to randomization; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term prophylactic use of corticosteroids for contrast agents, etc.;
• Patients with known active or suspected autoimmune diseases. Patients with autoimmune-related hypothyroidism and receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are eligible to be enrolled;
• Patients who have received live vaccine or live attenuated vaccine within 4 weeks prior to randomization;
• Patients who are known to have anaphylaxis to macromolecular protein preparations/monoclonal antibodies or are allergic to any component in the formulation of the investigational product;
• Patients with active tuberculosis;
• Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or history of organ transplantation;
• Patients with active HBV or HCV infection or HBV/HCV co-infection;
• Pregnant or lactating women;
• Patients who are not suitable for participating in this clinical study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator.