Black Diamond announces initial Phase 2 data of BDTX-1535

Black Diamond Therapeutics reported initial Phase 2 data demonstrating encouraging clinical responses and durability of BDTX-1535 in patients with relapsed/refractory epidermal growth factor receptor-mutant non-small cell lung cancer. Phase 2 preliminary data overview: The phase 2 trial began in August of 2023, and enrolled relapsed/refractory patients with non-classical EGFR mutations and those with C797S resistance mutations. Safety assessment and dose selection were based upon the first 40 patients randomized to receive BDTX-1535 once daily at either 100 mg or 200 mg across both Cohorts. Preliminary response rate and durability were assessed in 27 patients at 200 mg with an August 17, 2024, data cutoff, including 22 response-evaluable patients who met protocol eligibility criteria. Key takeaways: 200 mg daily selected for pivotal clinical development. Dose selection was based primarily on pharmacokinetics, safety and tolerability data from 20 patients at 100 mg, and 20 patients at 200 mg. Favorable tolerability profile at 200 mg, consistent with prior BDTX-1535 clinical data. The majority of adverse events were mild or moderate, and no new safety signals were observed. The most common on-target treatment-related adverse events were rash and diarrhea. There were 2 cases of grade 3 rash, and no reported cases of grade 4 rash or grade 3/4 diarrhea. Preliminary objective response rate of 42% achieved in 19 patients. For the 22 response-evaluable patients, the preliminary ORR was 36%. Nineteen of these 22 patients expressed known osimertinib resistance mutations: either C797S or P-loop alpha-C helix compressing. Of these 19 patients, 8 achieved a response: 5 with a confirmed partial response, including 1 patient who converted from a PR to an unconfirmed complete response at 8 months; and 3 with an unconfirmed PR at first scan and awaiting a confirmatory scan. An additional 9 patients experienced stable disease. Encouraging durability observed, with duration of response of approximately 8 months or more for first 3 patients with PR; 14 of 19 patients remain on therapy. Mean follow-up time is 4.7 months. Black Diamond continues to enroll patients in the second- and third-line cohorts, as well as in the first-line setting for patients with non-classical EGFR mutations. In Q1 2025, the Company expects to disclose initial results from the first-line cohort and to outline potential registrational paths in the recurrent setting based on FDA feedback.