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documented radiographically per RECIST 1.1, or (ii) a non-study anticancer treatment is initiated, or (iii) consent is withdrawn, or (iv) the participant becomes lost to follow-up.~Lenvatinib will not be stopped for complete response (CR); participants should remain on lenvatinib until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.
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.