Pembrolizumab/Vibostolimab (MK-7684A) or Atezolizumab in Combination With Chemotherapy in First Line Treatment of Extensive-Stage Small Cell Lung Cancer (MK-7684A-008/KEYVIBE-008)
- Conditions
- Small Cell Lung Carcinoma
- Interventions
- Biological: Pembrolizumab/Vibostolimab Co-FormulationDrug: Saline placebo
- Registration Number
- NCT05224141
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 460
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab 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. Atezolizumab Carboplatin 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. Atezolizumab Cisplatin 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. Pembrolizumab/Vibostolimab Pembrolizumab/Vibostolimab Co-Formulation 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. Pembrolizumab/Vibostolimab Saline placebo 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. Pembrolizumab/Vibostolimab Etoposide 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. Pembrolizumab/Vibostolimab Cisplatin 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. Pembrolizumab/Vibostolimab Carboplatin 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. Atezolizumab Saline placebo 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. Atezolizumab Etoposide 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to approximately 25 months PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). PFS was calculated using the nonparametric Kaplan-Meier method; participants who did not experience a PFS event were censored at the last disease assessment, or the last assessment before new anticancer treatment if new treatment was initiated. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented.
Objective Response Rate (ORR) Up to approximately 25 months ORR was defined as the percentage of participants in the analysis population who have a confirmed Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). The ORR was calculated using the Miettinen \& Nurminen method stratified by baseline ECOG performance status (0 or 1), baseline LDH (≤ or \> upper limit of normal \[ULN\]), and baseline presence of liver metastasis (Yes or No), or brain metastasis (Yes or No).
Duration of Response (DOR) Up to approximately 25 months For participants who demonstrated a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: ≥30% decrease in the sum of target lesion diameters without progression in other lesions) per RECIST 1.1, DOR was defined as the time from first documented CR or PR until progressive disease (PD) or death from any cause, whichever occurs first. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). DOR was calculated using the nonparametric Kaplan-Meier method for censored data.
Percentage of Participants Who Experienced an Adverse Event (AE) Up to approximately 60 months An AE is any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Percentage of Participants Who Discontinued Study Treatment Due to an AE Up to approximately 60 months An AE is any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
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 The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome.
Change From Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 Baseline and up to approximately 60 months The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function.
Change From Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 Baseline and up to approximately 60 months The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea.
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 The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing.
Change From Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 Baseline and up to approximately 60 months EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain.
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 The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of individuals with cancer. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 Baseline and up to approximately 60 months The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 Baseline and up to approximately 60 months The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 Baseline and up to approximately 60 months The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 Baseline and up to approximately 60 months The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Trial Locations
- Locations (140)
Infirmary Cancer Care ( Site 0022)
🇺🇸Mobile, Alabama, United States
Los Angeles Hematology Oncology Medical Group ( Site 0006)
🇺🇸Los Angeles, California, United States
VA West Los Angeles Medical Center ( Site 0004)
🇺🇸Los Angeles, California, United States
Boca Raton Regional Hospital-Lynn Cancer Institute ( Site 0014)
🇺🇸Boca Raton, Florida, United States
Fort Wayne Medical Oncology and Hematology ( Site 0013)
🇺🇸Fort Wayne, Indiana, United States
Dana-Farber Cancer Institute ( Site 0018)
🇺🇸Boston, Massachusetts, United States
Cancer and Hematology Centers of Western Michigan ( Site 0001)
🇺🇸Grand Rapids, Michigan, United States
Hattiesburg Clinic Hematology/Oncology ( Site 0003)
🇺🇸Hattiesburg, Mississippi, United States
Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0005)
🇺🇸Lancaster, Pennsylvania, United States
Blue Ridge Cancer Care ( Site 0015)
🇺🇸Blacksburg, Virginia, United States
Scroll for more (130 remaining)Infirmary Cancer Care ( Site 0022)🇺🇸Mobile, Alabama, United States