Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) for Advanced Melanoma in Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1)-Exposed Participants (MK-7902-004/E7080-G000-225/LEAP-004)

NCT03776136 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: 7902-004MK-7902-004E7080-G000-225LEAP-0042018-002518-10
• Study Type: interventional
• Target: 103
• Locations: 5 countries
• Sites: 23

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.

Conditions

Advanced Melanoma

Keywords

programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1); programmed cell death ligand 2 (PD-L2, PDL2)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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).

  Up to approximately 55 months

Secondary Outcomes (6)

• 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

Study Arms (1)

lenvatinib plus pembrolizumab

EXPERIMENTAL

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.

Drug: lenvatinib; Biological: pembrolizumab

Interventions

lenvatinib DRUG

Administered orally once a day during each 21-day cycle.

Also known as: MK-7902, E7080, LENVIMA™

lenvatinib plus pembrolizumab

pembrolizumab BIOLOGICAL

Administered as an IV infusion on Day 1 Q3W.

Also known as: MK-3475, Keytruda®

lenvatinib plus pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Has adequate organ function

You may not qualify if:

• 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
• Has a history of active tuberculosis (Bacillus tuberculosis)
• Has presence of a gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
• Has had major surgery within 4 weeks prior to first dose of study interventions (adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility)
• Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
• Has radiographic evidence of major blood vessel invasion/infiltration

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (23)

Ironwood Cancer & Research Centers ( Site 0312)

Chandler, Arizona, 85224, United States

Location

John Wayne Cancer Institute ( Site 0301)

Santa Monica, California, 90404, United States

Location

Advocate Medical Group-Park Ridge ( Site 0313)

Park Ridge, Illinois, 60068, United States

Location

Southeast Nebraska Cancer Center ( Site 0316)

Lincoln, Nebraska, 68510, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0317)

Dallas, Texas, 75246, United States

Location

Inova Schar Cancer Institute ( Site 0314)

Fairfax, Virginia, 22031-4867, United States

Location

Melanoma Institute Australia ( Site 0152)

Wollstonecraft, New South Wales, 2065, Australia

Location

Princess Alexandra Hospital ( Site 0154)

Woolloongabba, Queensland, 4102, Australia

Location

Box Hill Hospital ( Site 0157)

Box Hill, Victoria, 3128, Australia

Location

Fiona Stanley Hospital ( Site 0156)

Perth, Western Australia, 6150, Australia

Location

Lismore Base Hospital ( Site 0153)

Lismore, 2480, Australia

Location

Sunnybrook Research Institute ( Site 0654)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 0655)

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)

Montreal, Quebec, H2X 3E4, Canada

Location

McGill University Health Centre ( Site 0651)

Montreal, Quebec, H4A 3J1, Canada

Location

Hospital Clinic i Provincial Barcelona ( Site 0001)

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon ( Site 0003)

Madrid, 28007, Spain

Location

Hospital Universitario Virgen de la Macarena ( Site 0004)

Seville, 41009, Spain

Location

Hospital General Universitario de Valencia ( Site 0002)

Valencia, 46014, Spain

Location

Sahlgrenska Universitetssjukhuset ( Site 0052)

Gothenburg, 413 45, Sweden

Location

Skanes Universitetssjukhus ( Site 0053)

Lund, 221 85, Sweden

Location

Karolinska Universitetssjukhuset ( Site 0051)

Solna, 171 64, Sweden

Location

Norrlands Universitetssjukhus ( Site 0056)

Umeå, 901 85, Sweden

Location

Related Publications (1)

• Arance A, de la Cruz-Merino L, Petrella TM, Jamal R, Ny L, Carneiro A, Berrocal A, Marquez-Rodas I, Spreafico A, Atkinson V, Costa Svedman F, Mant A, Khattak MA, Mihalcioiu C, Jang S, Cowey CL, Smith AD, Hawk N, Chen K, Diede SJ, Krepler C, Long GV. Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. J Clin Oncol. 2023 Jan 1;41(1):75-85. doi: 10.1200/JCO.22.00221. Epub 2022 Jul 22.

  PMID: 35867951 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

lenvatinib; pembrolizumab

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: December 14, 2018
• Study Start: January 30, 2019
• Primary Completion: October 11, 2023
• Study Completion: October 11, 2023
• Last Updated: October 9, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

AU (5); CA (4); ES (4); US (6); SE (4)