A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Nonsquamous Non-small Cell Lung Cancer
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 201
- Locations
- 19
- Primary Endpoint
- Part 2: Overall Survival (OS)
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
The purpose of this study is to assess the safety and efficacy of pemetrexed+platinum chemotherapy+pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults from mainland China with metastatic nonsquamous non-small cell lung cancer.
The primary study hypotheses state that: 1) the combination of lenvatinib+platinum doublet chemotherapy+pembrolizumab prolongs Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST 1.1) compared to matching placebo+platinum doublet chemotherapy+pembrolizumab, and 2) the combination of lenvatinib+platinum doublet chemotherapy+pembrolizumab prolongs Overall Survival (OS) compared to matching placebo+platinum doublet chemotherapy + pembrolizumab.
Detailed Description
The China extension study will include participants previously enrolled in mainland China for the global study for MK-7902-006 (NCT03829319) plus those enrolled in mainland China as part of the China extension enrollment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer \[AJCC\], version 8 or current version) nonsquamous NSCLC.
- •Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated as primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat Sarcoma (KRAS) gene mutation).
- •Have measurable disease based on RECIST 1.
- •Note: Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
- •Provided an evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (that was not previously irradiated) for central PD-L1 testing.
- •Life expectancy of at least 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization.
- •Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and/or lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents. A male participant must also agree to the following: 1) abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR 2) agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- •Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) not a WOCBP OR 2) a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention.
- •Adequate organ function.
Exclusion Criteria
- •Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
- •History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
- •Radiographic evidence of major blood vessel invasion/infiltration.
- •Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. Note: The time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
- •Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
- •Has had allogeneic tissue/solid organ transplant.
- •Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
- •Known history of Hepatitis B or active Hepatitis C. No testing for Hepatitis B or Hepatitis C is required unless mandated by the local health authority.
- •History of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
Arms & Interventions
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib
Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.
Intervention: Pembrolizumab
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib
Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.
Intervention: Carboplatin
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib
Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.
Intervention: Cisplatin
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib
Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.
Intervention: Pemetrexed
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib
Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.
Intervention: Lenvatinib
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo
Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.
Intervention: Pembrolizumab
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo
Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.
Intervention: Carboplatin
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo
Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.
Intervention: Cisplatin
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo
Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.
Intervention: Pemetrexed
Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo
Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.
Intervention: Placebo matching lenvatinib
Outcomes
Primary Outcomes
Part 2: Overall Survival (OS)
Time Frame: Up to approximately 43 months
OS is defined as the time from randomization to the time of death from any cause. OS is presented.
Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 43 months
PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented.
Secondary Outcomes
- Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 57 months)
- Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 57 months)
- Part 2: Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 42 months)
- Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event(Up to approximately 42 months)