NCT05282901

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

A Phase II, Monocentric, Single Arm Trial Evaluating the Efficacy and Safety of Pembrolizumab in Combination With Lenvatinib in Metastatic Uveal MElanoma Patients

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 51 (actual)
• Sponsor: Institut Curie · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

After a screening phase of up to 28 days, each participant will receive assigned study intervention of pembrolizumab (maximum of 35 cycles) plus lenvatinib until reaching a discontinuation criterion including disease progression. 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. Participants who discontinue for reasons other than radiographic PD will have post-treatment follow-up imaging for disease status until (i) PD is documented radiographically per RECIST 1.1, or (ii) a non-study anticancer treatment is initiated, or (iii) consent is withdrawn, or (iv) the participant becomes lost to follow-up. Lenvatinib will not be stopped for complete response (CR); participants should remain on lenvatinib until the discontinuation criterion are met. All participants will be followed for OS until death, withdrawal of consent, loss to follow-up, or the end of the study. The survival status of all the participants will be collected at the date of the Last Visit of the Last Patient. Exploratory research on biomarkers of response or resistance will also be conducted.

Conditions

• Metastatic Uveal Melanoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab 25 MG/1 ML Intravenous Solution	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.

Timeline

• Start date: 2022-07-07
• Primary completion: 2026-10-30
• Completion: 2026-11-15
• First posted: 2022-03-16
• Last updated: 2025-11-24

Locations

1 site across 1 country: France