Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98)

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Arms A-E:

• Has histologically or cytologically confirmed diagnosis of ES-SCLC in need ofsecond-line therapy

• Has progressed on or after treatment with an anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb)administered as part of first-line platinum-based systemic therapy for ES-SCLC

• Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American JointCommittee on Cancer, Eighth Edition

• Has received 1 prior line of systemic therapy for small cell lung cancer (SCLC)

• If a woman of childbearing potential (WOCBP), participant must have a negativehighly sensitive pregnancy test within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study treatment

• Has measurable disease per RECIST 1.1 as assessed by local siteinvestigator/radiology and verified by BICR

• Has submitted an archival tumor tissue sample or newly obtained core,incisional, or excisional biopsy of a tumor lesion not previously irradiated

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1assessed within 7 days before allocation/randomization

• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligibleif they have received Hepatitis B virus (HBV) antiviral therapy for at least 4weeks and have undetectable HBV viral load before randomization

• Participants with history of Hepatitis C virus (HCV) infection are eligible ifHCV viral load is undetectable at screening

• Has a predicted life expectancy of >3 months

• Arms A-D:

• Male participants must be abstinent from heterosexual intercourse or agree touse contraception during treatment for at least 7 days after the last dose oflenvatinib. No contraception is required if the participant is receivingpembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab

• Female participants are not pregnant or breastfeeding and are not a WOCBP or ifare a WOCBP, are abstinent from heterosexual intercourse or are usingcontraception during the intervention period and for at least 120 days afterthe last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, orfavezelimab/pembrolizumab or 30 days after the last dose of lenvatinib,whichever occurs last

• Female participants must abstain from breastfeeding during the interventionperiod and for at least 120 days after the last dose of pembrolizumab,pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 7 daysafter the last dose of lenvatinib, whichever occurs last

• Has adequately controlled blood pressure (BP) with or without antihypertensivemedications, defined as BP ≤150/90 millimeters of mercury (mm Hg) with no change inantihypertensive medications within 1 week before allocation/randomization

• Arm E:

• If capable of producing sperm, the participant agrees to refrain from donatingsperm and abstain from penile-vaginal intercourse or use a penile/externalcondom when having penile-vaginal intercourse with a nonparticipant ofchildbearing potential who is not currently pregnant. The length of timerequired to continue contraception for the study intervention R-Dx-d is 120days

• If a person of childbearing potential (POCBP) must use a contraceptive methodthat is highly effective (with a failure rate of <1% per year), with low userdependency, or if they adhere to penile-vaginal intercourse abstinence as theirpreferred and usual lifestyle (abstinent on a long-term and persistent basis),during the intervention period and for at least the time needed to eliminatethe study intervention after the last dose of study intervention. In addition,the participant agrees not to donate eggs (ova, oocytes) to others orfreeze/store eggs during this period for the purpose of reproduction. Thelength of time required to continue contraception for the study interventionR-Dx-d is 210 days

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Arms A-E:

• Has received prior systemic anticancer therapy including investigational agentswithin 4 weeks before start of study treatment

• Has received prior radiotherapy within 2 weeks of start of study treatment

• Has received lung radiation therapy >30 Gray (Gy) within 6 months before thefirst dose of study treatment

• Has received a live or live attenuated vaccine within 30 days before the firstdose of study treatment

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Participants with brain metastases may participate only if they satisfyall of the following: completed treatment (e.g., whole brain radiation treatment,stereotactic radiosurgery, or equivalent) ≥14 days before the first dose of studyintervention; have no evidence of new or enlarging brain metastases confirmed bypost-treatment repeat brain imaging (using the same modality) performed ≥4 weeksafter pretreatment brain imaging; and are neurologically stable without the need forsteroids for ≥7 days before the first dose of study intervention as per local siteassessment. Participants with untreated brain metastases will be allowed if they areasymptomatic, the investigator determines there is no immediate CNS-specifictreatment required, there is no significant surrounding edema, and the brainmetastases are of 5 millimeter (mm) or less in size and 3 or less in number.

• Has a history of severe hypersensitivity reaction (≥Grade 3) to any study treatmentand/or any of its excipients

• Has an active autoimmune disease that has required systemic treatment in past 2years except replacement therapy (eg, thyroxine, insulin, or physiologiccorticosteroid)

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy

• Arms A-D:

• Has had major surgery within 3 weeks before first dose of study treatment

• Has a preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

• Has clinically significant cardiovascular disease or major arterialthromboembolic event within 12 months before first dose of study intervention,including New York Heart Association Class III or IV congestive heart failure,unstable angina, myocardial infarction, cerebral vascular accident, or cardiacarrhythmia associated with hemodynamic instability

• Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3weeks before the first dose of study treatment

• Has gastrointestinal malabsorption or any other condition that might affectoral study intervention absorption

• Has serious nonhealing wound, ulcer, or bone fracture within 28 days before thestart of study treatment

• Has any major hemorrhage or venous thromboembolic events within 3 months beforethe start of study treatment

• Has a history of inflammatory bowel disease

• Has a history of a gastrointestinal perforation within 6 months before thestart of study treatment

• Has a known history of, or active, neurologic paraneoplastic syndrome

• Has received prior therapy with a receptor tyrosine kinase (RTK) inhibitor oranti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4),anti-immunoglobulin-like transcript (ILT)-4, or anti-lymphocyte-activation gene 3 (LAG-3) agents

• Has received prior therapy with an anti-PD-1/L1 agent and was permanentlydiscontinued from that treatment due to a treatment-related adverse event

• Has received an investigational agent or has used an investigational devicewithin 4 weeks prior to study intervention administration

• Has radiographic evidence of encasement or invasion of a major blood vessel, orof intratumoral cavitation

• Has symptomatic ascites, pleural effusion, or pericardial effusion

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroidtherapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any otherform of immunosuppressive therapy within 7 days prior the first dose of studytreatment

• Has a known history of Human Immunodeficiency Virus (HIV) infection

• Has concurrent active HBV or HCV

• Has progressive disease as initial response to first-line systemic chemotherapyin combination with PD-1/L1 inhibitor for ES-SCLC

• Has had an allogenic tissue/solid organ transplant

• Arm E:

• Received prior treatment with a CDH6-targeted agent or an ADC that consists ofan exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumabderuxtecan, datopotamab deruxtecan)

• Has received an investigational agent or has used an investigational devicewithin 4 weeks (or 5 half-lives, whichever is shorter) prior to studyintervention administration

• Has Chronic steroid treatment (>10 mg/day prednisone [or equivalent] per day),except for inhaled steroids for asthma or COPD, mineralocorticoids (e.g.,fludrocortisone) for participants with orthostatic hypotension, topicalsteroids for mild skin conditions, low-dose supplemental corticosteroids foradrenocortical insufficiency, Premedication for treatment groups and/orpremedication in case of any hypersensitivity, or intra-articular steroidinjections

• Is an HIV-infected participants with a history of Kaposi's sarcoma and/orMulticentric Castleman's Disease