Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Chemotherapy as First-Line Treatment in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (MK-3475-B99/ KEYNOTE-B99)

Exclusion Criteria

• •Has had major surgery within 3 weeks before first dose of study interventions
• •Has a preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
• •Has urine protein ≥1 g/24 hours
• •Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multiple gated acquisition (MUGA) or echocardiogram (ECHO)
• •Prolongation of QT interval with Fridericia's correction (QTcF) interval to \>480 ms
• •Has clinically significant cardiovascular disease or major arterial thromboembolic 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 cardiac arrhythmia associated with hemodynamic instability
• •Has active hemoptysis within 3 weeks before the first dose of study intervention
• •Has gastrointestinal malabsorption or any other condition that might affect oral study intervention absorption
• •Has serious nonhealing wound, ulcer, or bone fracture within 28 days before first dose of study intervention
• •Has any major hemorrhage or venous thromboembolic events within 3 months before the first dose of study intervention. Participants with venous thrombosis diagnosed more than 3 months before the first dose of study intervention must be on stable doses of anticoagulants
• •Has a history of inflammatory bowel disease
• •Has a history of a gastrointestinal perforation within 6 months before the first dose of study intervention
• •Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease
• •Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• •Has received prior treatment (chemotherapy, radiotherapy, or surgical resection) including investigational agents for SCLC
• •Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study
• •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
• •Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. A participant that meets this exclusion criterion but is otherwise deemed eligible for the study may be randomized across the specific intervention groups.
• •Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who is clinically stable following treatment for these conditions is eligible
• •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 the first dose of study intervention
• •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following: a) Completed treatment at least 14 days before the first dose of study intervention b) Have no evidence of new or enlarging brain metastases confirmed by posttreatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and c) Are neurologically stable without the need for steroids for at least 7 days before the first dose of study intervention as per local site assessment. Participants with untreated brain metastases will be allowed if they are asymptomatic, the investigator determines there is no immediate CNS-specific treatment required, there is no significant surrounding edema, and the brain metastases are of 5 mm or less in size and 3 or fewer in number
• •Has a history of severe hypersensitivity reaction to any study intervention and/or any of its excipients
• •Has an active autoimmune disease that has required systemic treatment in past 2 years
• •Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• •Has a known history of, or active, neurologic paraneoplastic syndrome
• •Has an active infection requiring systemic therapy
• •Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B virus infection or an active Hepatitis C infection
• •Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, 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
• •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• •Has had an allogenic tissue/solid organ transplant