Sacituzumab Tirumotecan (MK-2870) as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-2870-008)

Prior treatment

• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• Received prior treatment with a TROP2-targeted ADC
• Received prior treatment with a topoisomerase I-containing ADC
• Arm 1: Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
• Arm 2: Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
• Arm 2: Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their advanced or metastatic NSCLC
• Arm 2: Has received radiation therapy to the lung that is \>30 Gy within 6 months of the first dose of study intervention
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
• Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Arm 2: 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 the first dose of study medication
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection

Other illness

• Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
• Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
• Arm 2: Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
• Known additional malignancy that is progressing or has required active treatment within the past 3 years
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Active infection requiring systemic therapy
• History of HIV infection
• Known psychiatric or substance abuse disorder
• A severe hypersensitivity reaction to treatment a monoclonal antibody/component of the study intervention

Lab values

• History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator

Other

• Has Grade ≥2 peripheral neuropathy
• Known active CNS metastases and/or carcinomatous meningitis

• Arm 1: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit.
• Arm 2: Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC (Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC, AJCC Staging Manual, version 8).
• Arm 2: Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy
• Arm 2: Has tumor tissue that demonstrates PD-L1 TPS ≥ 50% as determined by PD-L1 IHC 22C3 pharmDx assay by local laboratory
• If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (100 days for sacituzumab tirumotecan and 90 days for carboplatin \[no restriction for pembrolizumab\]) AND agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
• For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception
• Arm 1: Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
• Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
• Archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated has been provided
• Have a life expectancy of at least 3 months
• Have an ECOG performance status of 0 or 1 within 3 days before the start of study intervention