Efficacy and Safety of Pembrolizumab in Combination With Lenvatinib in Metastatic Uveal MElanoma Patients (PLUME)

NCT05282901 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IC 2020-06
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Because we suspect that the benefit of anti-PD-1 in metastatic UM patients could vary according to previous exposure to Tebentafusp (better efficacy of anti-PD-1 after Tebentafusp), the combination of pembrolizumab and lenvatinib will be assessed in two independent cohorts: cohort 1 with Tebentafusp-naive patients, and cohort 2 with patients previously treated by Tebentafusp. The study is a monocentric, phase II trial with a single-arm of treatment in each cohort. Liver MRI and chest-abdomen-pelvis CT will be performed every 9 weeks until progressive disease (PD), followed by a Follow-up visit within 28 days after last treatment intake. Survival status will be registered after patient discontinuation.

Conditions

Metastatic Uveal Melanoma

Keywords

Metastatic; Uveal; Melanoma; Immune; Response

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) according to RECIST 1.1 criteria

  PFS will be estimated as a crude rate at 27 weeks (+/- 2 weeks, i.e. 14 days) after the start of treatment. Will be considered progression events: objective clinical progression, radiological progression according to RECIST 1.1 criteria and death from any cause.

  After 9 cycles (i.e. 27 weeks +/- 2 weeks)

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From date of first study treaments intakes until the date of first documented progression assessed up to 30 months

• Objective response rate (ORR)

  After 9 cycles (i.e. 27 weeks +/- 2 weeks)

• Progression-free survival (PFS) using the iRECIST criteria

  After 9 cycles (i.e. 27 weeks +/- 2 weeks)

• Overall Survival (OS)

  From date of first study treatments intake until the date of death from any cause, assessed up to 100 months

Study Arms (1)

Metastatic Uveal MElanoma patients

EXPERIMENTAL

Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of metastatic uveal melanoma (UM)

Drug: Pembrolizumab 25 MG/1 ML Intravenous Solution

Interventions

Pembrolizumab 25 MG/1 ML Intravenous Solution DRUG

Taken together, we hypothesize that combining pembrolizumab with lenvatinib in metastatic UM may target essential cellular oncogenic pathways while normalizing tumor vascularization, thus allowing an increased infiltration of the tumor by immune cells and an improved immune response.

Also known as: Lenvatinib

Metastatic Uveal MElanoma patients

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of metastatic uveal melanoma (UM).
• (i) Not having been treated with Tebentafusp for cohort 1 (Tebentafusp-naive patients) OR (ii) Having been previously treated with Tebentafusp for cohort 2.
• Life expectancy \> 3 months.
• Male participants must agree to use contraception
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance
• Measurable disease based on RECIST 1.1. lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have provided a newly obtained (or archival if no systemic treatment since the sampling) core or excisional biopsy of a tumor lesion not previously irradiated.
• Patients with French Social Security in compliance with the French law relating to biomedical research
• All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to first administration of study drug.
• Have adequate organ function as defined in the protocol.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, and CD137) for metastatic UM.
• In contrast, prior therapy with Tebentafusp is permitted.
• Has recently received prior systemic anti-cancer therapy including investigational agents or biological agents \[eg cytokines, antibodies or small molecules kinase inhibitors within 3 weeks or nitrosoureas/mitomycin C within 6 weeks\] prior to allocation. Prior liver surgery or local treatment of metastases is allowed if there is an unequivocal progression.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Only mRNA vaccines are authorized to prevent SARS-CoV-2 infection (COVID-19) during the trial.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• 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 prior to the first dose of study drug.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or lenvatinib and/or any of their excipients.
• Has 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

Sponsors & Collaborators

• Institut Curie: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis; Melanoma

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Manuel Rodrigues, MD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Monocentric, phase II trial with a single-arm of treatment in two independent cohorts with Tebentafusp-naive patients, and with patients previously treated by Tebentafusp

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 16, 2022
• Study Start: July 7, 2022
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (1)