A Phase 1b/2 Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination with Investigational Agents for the Treatment of Participants With PD-1/L1-refractory Extensive-Stage Small Cell Lung Cancer in Need of Second-Line Therapy (KEYNOTE-B98)
- Conditions
- Participants with extensive-stage small cell lung cancerMedDRA version: 21.1Level: PTClassification code: 10041068Term: Small cell lung cancer extensive stage Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507687-38-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 80
Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of second-line therapy, Has submitted an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated where such sample exists, Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before allocation/randomization, Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization, Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening, Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week before allocation/randomization, Has a predicted life expectancy of >3 months, 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 Joint Committee on Cancer, Eighth Edition, Has received 1 prior line of systemic therapy for small cell lung cancer (SCLC), Male participants must be abstinent from heterosexual intercourse or agree to use contraception during treatment for at least 7 days after the last dose of lenvatinib. No contraception is required if the participant is receiving pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab, Female participants are not pregnant or breastfeeding and are not a woman of childbearing potential (WOCBP) or if are a WOCBP, are abstinent from heterosexual intercourse or are using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last, Female participants must abstain from breastfeeding during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 7 days after the last dose of lenvatinib, whichever occurs last, A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study treatment, Has measurable disease per RECIST 1.1 as assessed by local site investigator/radiology and verified by BICR
Has had major surgery within 3 weeks before first dose of study treatment, Has a known history of, or active, neurologic paraneoplastic syndrome, Has received prior therapy with a receptor tyrosine kinase (RTK) inhibitor or anti- 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 permanently discontinued from that treatment due to a treatment-related adverse event, Has received prior systemic anticancer therapy including investigational agents within 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 the first dose of study treatment, Has received a live or live attenuated vaccine within 30 days before the first dose of study treatment, Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration, Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation, Has symptomatic ascites, pleural effusion, or pericardial effusion, Has a preexisting =Grade 3 gastrointestinal or non-gastrointestinal fistula, 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 treatment, 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: completed treatment (e.g., whole brain radiation treatment, stereotactic radiosurgery, or equivalent) =14 days before the first dose of study intervention; have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging (using the same modality) performed =4 weeks after pretreatment brain imaging; and are neurologically stable without the need for steroids for =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 millimeter (mm) or less in size and 3 or less in number., Has a history of severe hypersensitivity reaction (=Grade 3) to any study treatment and/or any of its excipients, Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid), Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, Has an active infection requiring systemic therapy, 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 chemotherapy in combination with PD-1/L1 inhibitor for ES-SCLC, Has clinically significant cardiovascular disease or major arterial thromboembolic event within 12 months before fir
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1.To evaluate the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events<br>2.To estimate the objective response rate as assessed by blinded independent central review per RECIST 1.1;Secondary Objective: To evaluate progression-free survival as assessed by blinded independent central review according to RECIST 1.1, To evaluate duration of response as assessed by blinded independent central review according to RECIST 1.1;Primary end point(s): Number of Participants Experiencing Dose-Limiting Toxicities (DLTs), Number of Participants Who Experience at Least One Adverse Event (AE), Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE), Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1);Secondary end point(s):Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)