Pilot study evaluating the addition of cemiplimab in BRAF-mutant anaplastic thyroid cancer after progression on dabrafenib and trametinib.

Abstract

e18149 Background: Anaplastic thyroid cancer (ATC) is a rare but highly aggressive form of thyroid cancer. The FDA has approved the use of dabrafenib and trametinib (DT) in the treatment of ATC driven by a BRAF mutation (about 40-45% of all ATC’s) based on the ROAR study. Preclinical data suggests that DT alters the immune environment around ATCs, possibly making them more susceptible to immune checkpoint inhibitors like cemiplimab (Cemi), an antibody to PD-1. Based on concerns that it would be difficult to distinguish the benefit of adding Cemi to DT based on the data from DT alone, we planned a pilot study with Cemi being added to DT at the time of progression on DT alone. Methods: Single institution pilot study of patients with BRAFm ATC where Cemi was added to DT after any tumor growth on DT (RECIST progression not required). Biopsies done pre DT, post DT, pre Cemi, and post Cemi. Inclusion criteria included RECIST 1.1 measurable disease and no contraindication to immunotherapy. Steroids were allowed. Primary objective was response rate with target of at least 1 response in 12 patients. Results: Twelve patients on DT received at least one dose of Cemi. Median age was 75 years (range 51-91). 11/12 patients were male. 3 (25%) had prior RT to the neck. Patients median time on DT prior to Cemi was 4.9 months (range 2-10 months). In the 12 patients, response rate after starting Cemi was: 3 (25%) had a partial response, 6 (50%) had stable disease, and 3 (25%) had progression of disease. The median survival after starting Cemi was 6.1 months (0.9-32.4+ months) with 3 patients who are still alive as of 1/15/2025, including 2 of the 3 patients that had a partial response. Three patients (25%) were alive at 12 months after starting Cemi. Conclusions: The addition of Cemi to DT in ATC showed promising activity in a group of BRAF mutant ATC that did worse than expected on DT alone. Research biopsy analysis is pending. This data is promising enough to further explore the addition of Cemi to DT either at time of progression on DT or perhaps as initial therapy. (Study support from Regeneron and R01CA255211-01). Clinical trial information: NCT04238624 .