The FDA has granted fast track designation to BH-30643, a macrocyclic OMNI-EGFR inhibitor, for the treatment of patients with advanced or metastatic EGFR C797S–positive non–small cell lung cancer (NSCLC) whose disease has progressed following prior treatment with a third-generation EGFR TKI, according to a news release from BlossomHill Therapeutics.1
The company stated that the designation was based on the FDA's review of preliminary data for BH-30643 and reflects the agency's recognition of an unmet need in a molecularly defined population for which no oral targeted therapies are approved. The EGFR C797S mutation is a recognized on-target mechanism of acquired resistance to third-generation EGFR TKIs such as osimertinib (Tagrisso), and patients who develop it have limited targeted options.
“Fast Track designation is an important regulatory milestone and reflects FDA's recognition, based on its review of our preliminary data, of the potential for BH-30643 to address a significant unmet medical need in this molecularly defined population, for which no oral targeted therapies are approved,” Geoff Oxnard, MD, chief medical officer of BlossomHill Therapeutics, stated in the news release.
FDA Grants BH-30643 Fast Track Status for EGFR C797S+ NSCLC
- The FDA granted fast track designation to BH-30643, BlossomHill Therapeutics' oral OMNI-EGFR inhibitor, for advanced/metastatic EGFR C797S–positive NSCLC that has progressed after a third-generation EGFR TKI.
- BH-30643 is designed to overcome C797S-mediated resistance, a known on-target mechanism of resistance to TKIs like osimertinib, while remaining selective over wild-type EGFR in preclinical studies.
- The designation is based on preliminary data from the ongoing phase 1/2 SOLARA trial (NCT06706076), which is testing BH-30643 in roughly 675 patients with EGFR- or HER2-mutant NSCLC and includes a dedicated C797S resistance cohort.
“Receiving this designation reaffirms our confidence in the development strategy for BH-30643 as a novel EGFR inhibitor designed to overcome C797S-mediated resistance,” Oxnard added. “It also provides opportunities for more frequent engagement with FDA and potential access to other expedited programs, including potential eligibility for rolling review and accelerated approval, if applicable criteria are met.”
What is the mechanism of action of BH-30643?
BH-30643 is an investigational, orally bioavailable, noncovalent, macrocyclic, brain-active, mutant-selective OMNI-EGFR inhibitor. In preclinical studies, the agent demonstrated potent inhibitory activity across diverse EGFR mutation categories, including classical activating mutations, on-target resistance mutations such as C797S with or without T790M, atypical mutations, and exon 20 insertions, while maintaining marked selectivity over wild-type EGFR.
How was the phase 1/2 SOLARA trial (NCT06706076) designed?
The ongoing first-in-human, open-label, multicenter, non-randomized phase 1/2 SOLARA trial is evaluating the safety, tolerability, pharmacokinetics, and antitumor activity of BH-30643 in adults with locally advanced or metastatic NSCLC harboring EGFR or HER2 mutations, with an estimated enrollment of 675 patients.2 Eligible patients are 18 years of age or older with pathologically confirmed disease and EGFR mutations—classical, atypical, or exon 20 insertions—or HER2 mutations in kinase-domain exons 18 to 21; an ECOG performance status of 1 or less; and a life expectancy of at least 3 months.
In the phase 1 portion, BH-30643 monotherapy is administered orally during dose escalation and dose expansion to characterize dose-limiting toxicities and determine the recommended phase 2 dose; the phase 2 portion evaluates BH-30643 at that dose. Per the company, ongoing dose-expansion cohorts span both TKI-pretreated and TKI-naive settings, including a C797S resistance cohort, across more than 40 sites in 10 countries.1 The primary end point of the phase 2 portion is objective response rate by blinded independent central review, and secondary end points include safety, pharmacokinetic parameters, disease control rate, time to response, duration of response, progression-free survival, overall survival, and quality-of-life measures.2
References
- BlossomHill Therapeutics announces FDA fast track designation for BH-30643, a macrocyclic OMNI-EGFR inhibitor for the treatment of advanced EGFR C797S-positive NSCLC. News release. BlossomHill Therapeutics, Inc. August 18, 2026. Accessed August 18, 2026. https://ir.bhtherapeutics.com/news-releases/news-release-details/blossomhill-therapeutics-announces-fda-fast-track-designation-bh
- A study of BH-30643 in subjects with locally advanced or metastatic NSCLC harboring EGFR and/or HER2 mutations (SOLARA). ClinicalTrials.gov. Updated August 5, 2026. Accessed August 18, 2026. https://clinicaltrials.gov/study/NCT06706076
