Belzutifan Shows Promise in Advanced Solid Tumors, Especially ccRCC

Amajor oncogenic factor in RCC is hypoxia-inducible factor 2 (HIF-2). The HIF-2 inhibitor belzutifan has been shown to have antitumor efficacy in renal cell carcinoma, and it is currently licensed for use in patients (pts) with VHL illness who need therapy for RCC, CNS hemangioblastomas, or pNETs that do not require immediate surgery. Belzutifan has been shown to have a durable anticancer activity and an acceptable safety profile in extensively pretreated RCC, according to findings from the phase 1 LITESPARK-001 trial (NCT02974738). New information is reported after more than 3 years of follow-up for patients with ccRCC who are currently undergoing treatment. Patients recruited in the ccRCC cohort had received at least one prior therapy, had RECIST-measurable illness, had an ECOG PS of 0 or 1, had functional organs, and had a survival time of at least 6 months. Patients took 120 mg of oral belzutifan once daily. The primary goal was to prevent harm. Researchers also tracked PFS and DOR using RECIST v1.1 as their secondary end objective. The end of the collection of data was on July 15, 2021.

Only 9 out of 55 patients (16%) in the ccRCC cohort are still receiving treatment as of the data cutoff date of July 15, 2021, with the progression of the disease being the primary reason for discontinuation (n = 34; 62%). Patients had a median of three prior therapies (range, one to nine), with 39 (71%) having had prior VEGF and immunotherapy. Patients were monitored for a mean total of 41.2 months (range 38.2-47.7) during treatment and for 30 days following the last dosage. There were 22 pts (40%) who had grade 3 TRAEs. Anemia (n = 13; 24%) and hypoxia (n = 7; 13%) were the most often observed grade 3 TRAEs (10%). No serious TRAEs (level 4 or 5) were found. There was a 25% ORR with 1 CR (2% of the total) and 13 PRs (24% of the total); the DCR was 80%. The median duration of response (DOR) was not met (range: 3.1+ to 37.9+ months), and as of the data cutoff date, only 8 of 14 patients (57%) were still responding. The overall response rate (ORR) was 31% (4/13 patients with favorable risk; all PRs) and 24% (10/42 patients with intermediate/poor risk; 1 CR, 9 PRs) based on IMDC risk.

Patients at intermediate or poor risk had a DCR of 76%, whereas those at favorable risk had a DCR of 92%. Eight out of thirty-nine patients (ORR = 21%; 1 CR; 7 PR); DCR = 74% had a response after previous VEGF and immunotherapy. Six out of sixteen patients (ORR = 38%; all PRs); DCR = 94%) responded after not receiving prior VEGF/immunotherapy. The overall group had a median PFS of 14.5 months (95% CI, 7.3-22.1) and a PFS rate of 34% at 156 weeks (>36 months). Patients with advanced ccRCC previously treated with belzutifan monotherapy continued to show a high rate of disease control and lasting responses after a median follow-up of > 3 years for that continuing treatment. The safety profile of belzutifan was positive, and no unexpected safety signals were found. Multiple phase 3 studies are currently testing belzutifan for ccRCC, both as a monotherapy and in combination with other treatments.

Source: https://meetings.asco.org/abstracts-presentations/207892

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02974738

Eric Jonasch, Todd Michael Bauer, Kyriakos P. Papadopoulos, Elizabeth R. Plimack, Jaime R. Merchan, David F. McDermott, M. Dror Michaelson, Leonard Joseph Appleman, Ananya Roy, Yanfang Liu, Rodolfo F. Perini, Toni K. Choueiri/Phase 1 LITESPARK-001 (MK-6482-001) study of belzutifan in advanced solid tumors: Update of the clear cell renal cell carcinoma (ccRCC) cohort with more than 3 years of total follow-up/J Clin Oncol 40, 2022 (suppl 16; abstr 4509) DOI10.1200/JCO.2022.40.16_suppl.4509