RESEARCH STUDIES & Clinical Trials

Clinical Trial ID: NCT03820986 A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants with Advanced Melanoma (LEAP-003)

Status

Open

Description

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma. The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ

Objective

Primary objective is to compare progression-free survival (PFS) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Treatment

Experimental: Pembrolizumab+Lenvatinib Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years. Active Comparator: Pembrolizumab+Placebo Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.

Conditions

Melanoma, skin

Phases

III

Therapies

Drugs

Age Group

Adult

Main Investiagtor

Neki, Anterpreet

Practice

Melanoma

Scope

National

Participating Institutions

Baptist MD Anderson Cancer Center

Eligibility

Inclusion Criteria: Has histologically or cytologically confirmed melanoma Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy Has been untreated for advanced or metastatic disease except as follows: a. proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. b. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [anti-PD-1] therapy or Interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation. Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization. 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 contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period Female participants must not be pregnant, not breastfeeding, and ≥1 of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) OR b. A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1 Has adequate organ function 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. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy. Has known active central nervous system 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 (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 not considered a form of systemic treatment. Has an active infection requiring systemic therapy Has known history of human immunodeficiency virus (HIV) infection Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Nct ID Number

NCT03820986

Secondary Trial ID Number

MK-7902-003-01/LEAP-003

Keywords

Treatment

More Information

clinicaltrials.gov

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