Clinical trials

Uveal melanoma (UM) is a rare type of melanoma, with an incidence of 4.4 cases per million in Europe each year. During recent years, different treatment approaches have been tested in patients with metastatic UM. Responses have been reported primarily with localized treatment in patients with a limited number of liver metastases. In cases of diffuse liver involvement or extrahepatic disease, systemic therapies are justified. However, to date, systemic therapies such as targeted therapy with selumetinib or conventional chemotherapy have failed in metastatic UM. Neo-TB is a Phase II, single arm, multicentre clinical trial designed to evaluate efficacy and safety of tebentafusp used as a single agent in patients with metastatic uveal melanoma with resectable / potentially resectable liver metastasis and absence of extrahepatic disease. The main questions it aims to answer are: 1. Which is the capacity of tebentafusp used as a single agent to generate pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable liver metastasis and absence of extrahepatic disease. 2. Which is the efficacy of tebentafusp used as a single agent to maintain disease control and delay relapse / progression. 3. Which is the safety of tebentafusp used as a single agent in metastatic uveal melanoma. The main hypothesis is that neoadjuvant treatment with Tebentafusp could achieve ≥20% pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable/potentially resectable liver metastasis and absence of extrahepatic disease. It is assumed that untreated patients would not present a pCR (response rate of ≤1%).

Brain metastases in patients with advanced and metastatic melanoma are a frequent complication and a significant cause of morbidity and mortality in this patient population. As the incidence of brain metastases continues to increase in patients with metastatic melanoma, it is urgent that the investigators identify effective therapies. ENCEFALO is a Phase II, single arm, multicentre clinical trial designed to evaluate the activity of encorafenib plus binimetinib followed by cemiplimab and fianlimab in patients with BRAF mutated melanoma and symptomatic brain metastases, following the simon design Two-stage minimax. The objective main is to evaluate the 6 month intracranial progression-free survival (icPFS) proportion of Encorafenib plus Binimetinib followed by Cemiplimab plus Fianlimab in patients with BRAF-mutated melanoma and symptomatic brain metastases according RECIST criteria The trial hypothesis is: For patients with BRAF-mutated melanoma and symptomatic brain metastases, an induction treatment with encorafenib and binimetinib (EB) for about two months (i.e. 8 weeks) followed by cemiplimab plus fianlimab (CF) would allow a 6 month icPFS rate of 40% in comparison to historical control of 20% based on CM204 symptomatic arm (Tawbi et al 2021).

There is a lack of strategies for patients who progress after responding to PD-1/l-1 in melanoma. High expression of Nectin4 in skin and melanomas may serve as a new target in advanced melanomas. The combination of enfortumab/vedotin (EV) and pembrolizumab has shown synergistic effect in various solid tumors. Enfortumab vedotin and pembrolizumab may have a dual effect on clinical outcomes. PLUGIN is a multicenter, non-randomized open-label, 2-cohort, phase 2 study to evaluate the ORR of pembrolizumab in combination with enfortumab vedotin (EV) in previously treated participants with unresectable stage III or IV melanoma and disease progression on standard therapy. The primary objective is evaluate the efficacy of enfortumab/vedotin and pembrolizumabplus pembrolizumab in advanced melanoma. Hypothesis: 1) High expression of Nectin4 in skin and melanomas may serve as a new target in advanced melanomas; 2)EV+Pembrolizumab has shown synergistic effect in various solid tumors; 3) There is a lack of strategies for patients who respond to PD1-mAbs in melanoma. Primary Endpoint: Objective Response Rate (ORR) as assessed by the investigator according RECIST 1.1 A total of 60 patients will be enrolled in this study to evaluate efficacy and outcomes in two different cohorts: Cohort 1: patients who did not have BRAF mutation V600E and had disease progression on immune (IO) therapy. Cohort 2, patients with activating BRAF mutations, must have progressed on IO therapy and BRAF/MEKi

This is an observational, multicentre epidemiological study with a longitudinal cohort in which information will be retrieved from medical records of patients with advanced metastatic or unresectable melanoma at first diagnosis.