On the third day of ESMO 2021, Merck presented the results from the ongoing phase II trial of belzutifan (Welireg) in combination with cabozantinib (Cabometyx) in advanced ccRCC patients (Abstract #656MO). The trial is being conducted in two cohorts. Cohort 1 includes advanced ccRCC patients who have not received any previous therapy for the disease, while cohort 2 is being conducted in advanced ccRCC patients who have received no more than two prior treatments or immunotherapy. The mini oral presentation showed results of cohort 2, which enrolled 52 patients. From the 52 patients included in the analysis with a median follow-up of 15.4 months, 86.5% of the patients experienced a reduction in target lesion size and the ORR was 28.8%, observed in 15 of 52 patients, while the DCR was 92.3%, observed in 48 of 52 patients. Grade 3-5 TRAEs was seen in 65.4% patients. Moreover, 26.9% patients had serious TRAEs and was one death from TRAEs.
Insights- The data presented at ESMO 2021 demonstrated that treatment with belzutifan and cabozantinib had potential antitumor activity in previously treated patients with advanced ccRCC, while the preliminary results from Cohort 2, presented by Merck during ASCO 2021, were also satisfactory. We already know that Cabozantinib alone is associated with a 20% ORR in 1L RCC, specifically in patients with intermediate/poor risk criteria, therefore, we expect the combined promising results from both ASCO and ESMO 2021, could help this drug combination in providing a smooth pathway for regulatory submission in the future, and could possibly follow a path similar to that of belzutifan’s approval in VHL- associated RCC. Moreover, the company is also recruiting for a phase III trial of belzutifan in combination with lenvatinib versus cabozantinib for the same patient population, while a phase I/II combination trial of pembrolizumab with cabozantinib in patients with metastatic RCC is also ongoing.
