Clinical Summary: 

• Design/Population: An ongoing dose-escalation study evaluated HSK42360, a next-generation brain-penetrant BRAF paradox breaker, in 69 patients with advanced BRAF V600-mutant solid tumors, including patients with primary CNS tumors.
• Key Outcomes: HSK42360 demonstrated an ORR of 40.9% in CNS tumors, with higher responses observed in low-grade glioma. Treatment was well tolerated, with mostly low-grade adverse events and no dose-limiting toxicities.
• Clinical Relevance: HSK42360 demonstrates promising activity and favorable tolerability in BRAF V600-mutant gliomas, addressing limitations of current BRAF inhibitors. These results support further development as a next-generation, CNS-active targeted therapy.

Results from a phase 1 study demonstrate that HSK42360, a next-generation brain-penetrant BRAF paradox breaker, shows promising clinical activity with favorable safety among patients with BRAF V600-mutant gliomas.

These findings were presented by Shidong Gao, MD, PhD, Haisco Pharmaceutical Group Co Ltd, Chengdu, China, at the 2026 American Association for Cancer Research (AACR) Annual Meeting in San Diego, California. 

In this dose-escalation trial, 69 patients with advanced BRAF V600-mutated solid tumors received once daily HSK42360 at doses ranging from 200 to 3600 mg. The primary end point was safety. A key secondary end point was objective response rate (ORR) in patients with primary CNS tumors (n = 22). 

At the data cutoff point, no dose-limiting toxicities, treatment-related discontinuations, or deaths were reported. Treatment-related adverse events occurred in 81.2% of patients and were predominantly grade 1. The most frequently reported adverse events included ALT increase (23.2%), AST increase (23.2%), and anemia (20.3%). 

Among patients with primary CNS tumors evaluable for efficacy, the ORR was 40.9%, with 1 complete response. Patients with high-grade glioma had an ORR of 36.8% and patients with low-grade glioma had an ORR of 66.7%.

“HSK42360 demonstrated significant efficacy… along with promising clinical antitumor activity in BRAF V600-mutant glioma patients, both treatment-naïve and previously treated with BRAF inhibitors,” concluded Dr Gao et al. “It was well-tolerated with a manageable safety profile, offering a new therapeutic paradigm for BRAF-mutant glioma.” 

Source: 

Gao S, Qian M, Wang J, et al. Novel brain-penetrant BRAF paradox breaker HSK42360 demonstrates promising antitumor activity in patients with BRAF-mutant glioma. Presented at AACR Annual. April 17 - 22, 2026; San Diego, California. LB405.