A Phase 3, Randomized, Double-blind, Multicenter Study of MK-1084 in Combination With Pembrolizumab Compared With Pembrolizumab Plus Placebo as Firstline Treatment of Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic NSCLC With PD-L1 TPS ≥50% (KANDLELIT-004)
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 600
- Locations
- 423
- Primary Endpoint
- Progression-Free Survival (PFS)
Overview
Brief Summary
This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There are two primary study hypotheses:
Hypothesis 1: Combination of calderasib and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
Hypothesis 2: Combination of calderasib plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The main inclusion and
Exclusion Criteria
- •include but are not limited to the following:
- •Inclusion Criteria:
- •Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
- •Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
- •Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research
- •If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to \< Grade 1 or baseline
- •If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)
- •If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
- •If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable
- •Exclusion Criteria:
Arms & Interventions
Placebo with Pembrolizumab
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.
Intervention: Placebo (Other)
Placebo with Pembrolizumab
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.
Intervention: Pembrolizumab (Biological)
Calderasib with Pembrolizumab
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met.
Intervention: Calderasib (Drug)
Calderasib with Pembrolizumab
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met.
Intervention: Pembrolizumab (Biological)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Up to approximately 42 months
PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.
Overall Survival (OS)
Time Frame: Up to approximately 56 months
OS is defined as the time from randomization to death due to any cause.
Secondary Outcomes
- Number of Participants Who Experience One or More Adverse Event (AEs)(Up to approximately 56 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score(Baseline and Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 42 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score(Baseline and Up to approximately 24 months)
- Objective Response Rate (ORR)(Up to approximately 42 months)
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)(Up to approximately 56 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Chest pain (Item 40) Score(Baseline and Up to approximately 24 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) Chest pain (Item 40) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score(Baseline and Up to approximately 24 months)
- Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score(Baseline and Up to approximately 24 months)