Blueprint Medicines Corporation announced proof-of-concept data from the Phase 1/2 SYMPHONY clinical trial of BLU-945, an investigational precision therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC). The trial results showed early evidence of safety and clinical activity consistent with preclinical data, supporting plans to expand development of BLU-945 in combination with multiple agents including osimertinib, with the goal of preventing or treating tumor resistance to prolong patient benefit. The data were reported at the American Association for Cancer Research (AACR) Annual Meeting 2022 in New Orleans.

Early data from the ongoing Phase 1 dose escalation part of the SYMPHONY trial showed dose-dependent decreases in circulating tumor DNA (EGFR variant allele fractions) and radiographic tumor reductions, including a partial response (PR) in a patient treated with 400 mg once daily (QD), a high dose tested as of the data cutoff date. Pharmacokinetic results showed BLU-945 exposures at higher doses were associated with broad EGFR mutation coverage, including the activating L858R mutation with or without the osimertinib-resistant C797S mutation. BLU-945 was generally well-tolerated, with no significant adverse events (AEs) associated with wild-type EGFR inhibition.

The maximum tolerated dose and recommended Phase 2 dose have not yet been identified, and dose escalation is continuing.