BlossomHill's BH-30643 hits 45% response rate in C797S NSCLC
BlossomHill Therapeutics has presented updated efficacy and safety data for BH-30643, its investigational EGFR inhibitor, at the IASLC 2026 World Conference on Lung Cancer in Seoul. The results, drawn from the ongoing Phase 1/2 SOLARA trial, centre on a particularly difficult-to-treat group: patients whose tumours carry the EGFR C797S resistance mutation after failure on a prior EGFR inhibitor, with or without the concurrent T790M mutation.
Among 40 patients in this cohort, BH-30643 produced an objective response rate (ORR) of 45% (18 of 40 patients; 95% CI: 29%–62%) and a disease control rate of 88% (35 of 40). At the time of efficacy follow-up, 63% of patients remained on treatment, with a median follow-up of 6.9 months. Patients had received a median of two prior lines of therapy; 98% had previously received osimertinib, and 53% had a history of brain metastases, reflecting a heavily pretreated population.
Safety and tolerability
The safety dataset at expansion doses of 40 mg, 50 mg and 60 mg twice daily covered 174 patients. Treatment-related dose reductions occurred in 9% of patients, and discontinuations in 3%, rates the company described as low. The most common treatment-related adverse event was bilirubin elevation, characterised as generally asymptomatic and predominantly unconjugated, consistent with inhibition of the UGT1A1 enzyme. EGFR wild-type-associated adverse events were primarily Grade 1.
Hidehito Horinouchi, of the National Cancer Center Hospital in Tokyo and the study's presenting author, said: "The responses observed with BH-30643 in this heavily pretreated population, together with encouraging early evidence of durability, support the potential of BH-30643 to directly target this resistance mechanism."
Geoff Oxnard, Chief Medical Officer at BlossomHill, noted the results span "a molecularly diverse group of patients with C797S-positive disease, including patients with concurrent T790M and those who have received multiple prior therapies." The company received FDA Fast Track designation for BH-30643 in the C797S-positive advanced or metastatic NSCLC setting ahead of the conference. A global Phase 2 study targeting this population is planned to initiate in the first quarter of 2027.
Market context and competitive landscape
C797S-mediated resistance to third-generation EGFR inhibitors, principally osimertinib, has been a recognised clinical problem for over a decade. Despite this, no targeted therapy is approved for this mutation, leaving patients with limited options beyond chemotherapy or antibody-drug conjugates. Several programmes are in development to address on-target osimertinib resistance, including allosteric and fourth-generation covalent approaches from both large pharma and clinical-stage biotechs, making this one of the more active corners of thoracic oncology drug development.
BH-30643's macrocyclic, non-covalent structure is presented by the company as offering selectivity over wild-type EGFR, which underpins the relatively clean tolerability profile seen to date. The drug also claims brain-penetrant activity, a meaningful attribute given the high rate of central nervous system involvement in EGFR-mutant NSCLC. Whether the 45% ORR and durability data hold in a larger, confirmatory Phase 2 cohort will be the critical question for investors and clinicians. Median duration of response has not yet been reported, and the 6.9-month follow-up is still early for a resistance indication where progression patterns can be complex.
BlossomHill, which listed on NASDAQ in August 2026, is also developing BH-30236, a CLK inhibitor in AML and myelodysplastic syndromes, and BH-501284, a preclinical pan-KRAS inhibitor, though BH-30643 remains the lead programme and the principal focus for near-term clinical milestones.