A Multicenter, Open-label, Phase 2 Trial to Assess the Efficacy and Safety of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Melanoma Previously Exposed to an Anti-PD-1/L1 Agent (LEAP-004)
Overview
- Phase
- Phase 2
- Intervention
- pembrolizumab
- Conditions
- Advanced Melanoma
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 103
- Locations
- 23
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study will evaluate the safety and efficacy of combination therapy of lenvatinib (E7080/MK-7902) and pembrolizumab following approximately 2 years of pembrolizumab therapy and approximately 2 years or more lenvatinib therapy in adult participants with unresectable or advanced melanoma who have been exposed to anti-programmed cell death ligand 1 (PD-1/L1) agents approved for unresectable or metastatic melanoma. No statistical hypothesis will be tested in this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Has histologically or cytologically confirmed melanoma
- •Has unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8 that is not amenable to local therapy
- •Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 as confirmed by BICR.
- •Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
- •Has submitted pre-trial imaging
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Has provided a baseline tumor biopsy
- •Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of \>30 Gray (Gy), they must have recovered from the toxicity and/or complications from the Intervention
- •Male participants must agree to use approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period
- •Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention
Exclusion Criteria
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
- •Has a known additional malignancy that is progressing or requires active treatment
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has ocular melanoma
- •Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- •Has an active infection requiring systemic therapy
- •Has known history of Human Immunodeficiency Virus (HIV) or HIV 1/2 antibodies
- •Has known history of or is positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (HCV RNA qualitative\] is detected)
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
Arms & Interventions
lenvatinib plus pembrolizumab
Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
Intervention: pembrolizumab
lenvatinib plus pembrolizumab
Participants receive lenvatinib 20 mg orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
Intervention: lenvatinib
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to approximately 55 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).
Secondary Outcomes
- Progression-free Survival (PFS)(Up to approximately 55 months)
- Overall Survival (OS)(Up to approximately 55 months)
- Duration of Response (DOR)(Up to approximately 55 months)
- Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)(Cycle 1 Day 1: 0.5 to 4 hours and 6 to 10 hours postdose; Cycle 1 Day 15: Predose and 2 to 12 hours postdose; Cycle 2 Day 1: Predose, 0.5 to 4 hours, and 6 to 10 hours post-dose (each cycle =21 days))
- Number of Participants Who Experience At Least One Adverse Event (AE)(Up to approximately 55 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 48 months)