A Phase 3, Randomized, Double-Blind Study of MK-7684A in Combination With Etoposide and Platinum Followed by MK-7684A vs Atezolizumab in Combination With Etoposide and Platinum Followed by Atezolizumab for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer (KEYVIBE-008)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 460
- 试验地点
- 140
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study will evaluate the combination of a fixed dose pembrolizumab/vibostolimab co-formulation (MK-7684A) with etoposide/platinum chemotherapy followed by MK-7684A compared to the combination of atezolizumab with etoposide/platinum chemotherapy followed by atezolizumab in the first-line treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC). The primary hypothesis is, with respect to overall survival, MK-7684A in combination with the background therapy of etoposide/platinum followed by MK-7684A, is superior to atezolizumab in combination with the background therapy of etoposide/platinum followed by atezolizumab.
详细描述
With Amendment 4, the experimental Pembrolizumab/Vibostolimab arm (MK-7684A) was discontinued and all ongoing participants were offered an option to move to the comparator Atezolizumab monotherapy arm for the remainder of the study. There will be no further analyses of efficacy, and no European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) and Lung Cancer 13 module (EORTC QLQ-LC13) outcome measures will be reported.
Effective as of Amendment 5, participants with access to approved standard of care (SOC) should be considered for discontinuation from the study. Those benefiting from atezolizumab, but unable to access it as SOC outside the study, may continue on study and receive treatment with atezolizumab until discontinuation criteria are met.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Has histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC) in need of first-line therapy
- •Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition or T3-T4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan
- •Males agree to use contraception, refrain from donating sperm, and abstain from heterosexual intercourse
- •Females are not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP) or is a WOCBP who uses a highly effective contraceptive method, or is abstinent from heterosexual intercourse
- •Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
- •Has a predicted life expectancy of >3 months
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Is considered a poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease
- •Has received prior treatment for Small Cell Lung Cancer (SCLC)
- •Is expected to require any other form of antineoplastic therapy for SCLC while on study
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
- •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
- •Has a history of severe hypersensitivity reaction (≥Grade 3) 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
- •Has a known history of Hepatitis B or known active Hepatitis C virus infection
- •Has had an allogenic tissue/solid organ transplant
- •Has had major surgery within prior 3 weeks or has not recovered adequately from toxicity and/or complications from an intervention prior to receiving the first dose of study intervention
- •Has symptomatic ascites or pleural effusion
研究组 & 干预措施
Pembrolizumab/Vibostolimab
Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation (FDC) of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W) via intravenous (IV) infusion, in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve [AUC] 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A (200 mg vibostolimab/200 mg pembrolizumab FDC) Q3W via IV infusion, until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Pembrolizumab/Vibostolimab Co-Formulation (Biological)
Pembrolizumab/Vibostolimab
Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation (FDC) of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W) via intravenous (IV) infusion, in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve [AUC] 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A (200 mg vibostolimab/200 mg pembrolizumab FDC) Q3W via IV infusion, until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Saline placebo (Drug)
Pembrolizumab/Vibostolimab
Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation (FDC) of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W) via intravenous (IV) infusion, in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve [AUC] 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A (200 mg vibostolimab/200 mg pembrolizumab FDC) Q3W via IV infusion, until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Etoposide (Drug)
Pembrolizumab/Vibostolimab
Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation (FDC) of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W) via intravenous (IV) infusion, in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve [AUC] 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A (200 mg vibostolimab/200 mg pembrolizumab FDC) Q3W via IV infusion, until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Cisplatin (Drug)
Pembrolizumab/Vibostolimab
Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation (FDC) of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W) via intravenous (IV) infusion, in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve [AUC] 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A (200 mg vibostolimab/200 mg pembrolizumab FDC) Q3W via IV infusion, until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Carboplatin (Drug)
Atezolizumab
Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W via IV infusion, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab (1200mg atezolizumab) Q3W via IV infusion until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Saline placebo (Drug)
Atezolizumab
Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W via IV infusion, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab (1200mg atezolizumab) Q3W via IV infusion until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Etoposide (Drug)
Atezolizumab
Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W via IV infusion, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab (1200mg atezolizumab) Q3W via IV infusion until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Cisplatin (Drug)
Atezolizumab
Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W via IV infusion, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab (1200mg atezolizumab) Q3W via IV infusion until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Atezolizumab (Biological)
Atezolizumab
Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W via IV infusion, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab (1200mg atezolizumab) Q3W via IV infusion until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 25 months
Overall Survival (OS) was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was calculated using the nonparametric Kaplan-Meier method for censored data.
次要结局
- Change From Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13(Baseline and up to approximately 60 months)
- Progression-Free Survival (PFS)(Up to approximately 25 months)
- Objective Response Rate (ORR)(Up to approximately 25 months)
- Duration of Response (DOR)(Up to approximately 25 months)
- Percentage of Participants Who Experienced an Adverse Event (AE)(Up to approximately 60 months)
- Percentage of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 60 months)
- Change From Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline and up to approximately 60 months)
- Change From Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 60 months)
- Change From Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30(Baseline and up to approximately 60 months)
- Change From Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)(Baseline and up to approximately 60 months)
- Time to True Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 60 months)
- TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 60 months)
- TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30(Baseline and up to approximately 60 months)
- TTD in Cough Score (Item 31) on the EORTC QLQ-LC13(Baseline and up to approximately 60 months)
- TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13(Baseline and up to approximately 60 months)