BlossomHill Therapeutics has initiated expansion cohorts of its SOLARA trial, marking a significant milestone in the development of BH-30643, a first-in-class OMNI-EGFR inhibitor designed to overcome current limitations in EGFR-mutant non-small cell lung cancer (NSCLC) treatment. The company announced that the first patient has been dosed in the expansion phase of this global Phase 1/2 clinical trial.
Novel Mechanism Targets Broad EGFR Mutation Spectrum
BH-30643 represents a departure from conventional EGFR inhibitor design as a macrocyclic, non-covalent, mutant selective inhibitor. The drug demonstrates sub-nanomolar potency against both classical and atypical EGFR mutations, with activity maintained even in the presence of T790M and C797S resistance mutations that commonly emerge during treatment with existing therapies.
"When designing BH-30643, we pursued a different and broader ambition - a highly potent drug capable of inhibiting a wide spectrum of EGFR mutations, while sparing inhibition of wildtype EGFR and HER2, expected to provide a significant survival benefit and a better tolerated therapy for more patients," said J. Jean Cui, Ph.D., President and Chief Executive Officer of BlossomHill Therapeutics.
SOLARA Trial Design and Objectives
The SOLARA trial (NCT06706076) is evaluating BH-30643 in patients with locally advanced or metastatic NSCLC bearing EGFR or HER2 mutations. The expansion cohorts will assess single-agent objective response rate (ORR) across diverse EGFR mutation subtypes, including patients who have not received prior EGFR targeted therapy.
The transition to expansion cohorts follows successful completion of dose escalation, which demonstrated favorable pharmacokinetic and tolerability profiles along with preliminary anti-tumor activity in previously treated EGFR-mutant NSCLC patients.
Addressing Treatment Resistance Challenges
Current EGFR-targeted therapies face significant challenges from acquired resistance mutations, particularly T790M and C797S, which limit treatment durability. BH-30643's design specifically addresses these resistance mechanisms while maintaining selectivity against mutant EGFR variants.
"The increasing diversity of EGFR mutations has led to a growing number of therapeutic agents targeting various, narrowly defined subsets of EGFR mutation-positive lung cancer," noted Cui. The company's approach seeks to consolidate treatment options into a single, broadly active agent.
Clinical Development Strategy
Dr. Geoff Oxnard, Chief Medical Officer of BlossomHill Therapeutics, emphasized the strategic importance of the expansion phase: "Enrollment of the SOLARA expansion cohorts will be a critical step toward achieving that goal, allowing us to characterize drug activity across a diversity of targeted therapy pretreated and targeted therapy naive patient populations."
The expansion cohorts will provide crucial efficacy data across different patient populations, including both treatment-experienced and treatment-naive patients with various EGFR mutation subtypes. This comprehensive approach aims to establish BH-30643's potential as a first-line and later-line treatment option.
Company Pipeline and Focus
BlossomHill Therapeutics is developing a pipeline of small molecule candidates targeting oncology and autoimmune diseases. Beyond BH-30643, the company's clinical portfolio includes BH-30236 for relapsed or refractory acute myeloid leukemia and higher-risk myelodysplastic syndrome. The San Diego-based company is backed by investors including Cormorant Asset Management, OrbiMed, Vivo Capital, and Colt Ventures.
