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.
Brief Title
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)
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Small Cell Lung Carcinoma
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Exclusion Criteria:
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
Inclusion Criteria
Inclusion Criteria:
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 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05224141
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
7684A-008
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Up to approximately 25 months
Secondary Ids
Secondary Id
MK-7684A-008
Secondary Id
KEYVIBE-008
Secondary Id
jRCT2021220008
Secondary Id
2023-503517-30-00
Secondary Id
U1111-1287-4436
Secondary Id
2021-005034-42
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to approximately 25 months
Outcome Measure
Progression-Free Survival (PFS)
Outcome Description
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).
Outcome Time Frame
Up to approximately 25 months
Outcome Measure
Objective Response Rate (ORR)
Outcome Description
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.
Outcome Time Frame
Up to approximately 25 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
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.
Outcome Time Frame
Up to approximately 60 months
Outcome Measure
Percentage of Participants Who Experienced an Adverse Event (AE)
Outcome Description
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.
Outcome Time Frame
Up to approximately 60 months
Outcome Measure
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
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)
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
Change From Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
Change From Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
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)
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
Change From Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
Time to True Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
TTD in Cough Score (Item 31) on the EORTC QLQ-LC13
Outcome Description
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.
Outcome Time Frame
Baseline and up to approximately 60 months
Outcome Measure
TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone