BlossomHill's OMNI-EGFR Inhibitor BH-30643 Yields 45% ORR in C797S-Positive NSCLC
核心洞察
Updated Phase 1/2 SOLARA data show BH-30643 achieved a 45% objective response rate and 88% disease control rate in EGFR (搜索) C797S-positive NSCLC resistant to prior EGFR inhibitors.
Among 40 patients with C797S-positive disease, 63% remained on treatment at a median follow-up of 6.9 months, with 98% having received prior osimertinib.
BH-30643 showed a favorable safety profile at 40-60 mg twice daily, with treatment-related dose reductions in 9% and discontinuations in 3% of 174 patients.
BlossomHill Therapeutics (搜索), Inc. (Nasdaq: BLSM) reported updated results from the ongoing Phase 1/2 SOLARA trial showing that its investigational OMNI-EGFR (搜索)™ inhibitor BH-30643 produced a 45% objective response rate (ORR; 18/40) and an 88% disease control rate (DCR; 35/40) in patients with EGFR C797S-positive resistance to prior EGFR inhibitor therapy, with or without concurrent T790M. The data were presented in a mini-oral session at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer in Seoul, South Korea.
The company noted that C797S-positive disease represents a difficult-to-treat population with no approved targeted therapies. "C797S-driven resistance to third-generation EGFR (搜索) inhibitors was first described over 10 years ago, yet patients whose tumors develop this mutation currently have no approved targeted treatment options," said Hidehito Horinouchi, M.D., Ph.D., of the National Cancer Center Hospital, Tokyo, and presenting author of the study. "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."
Response Details and Patient Population
As of the May 12, 2026 data cutoff, with efficacy follow-up through August 10, 2026, 18 of 40 patients with EGFR (搜索) C797S-positive resistance achieved a confirmed (16) or ongoing unconfirmed (2) partial response, corresponding to an ORR of 45% (95% CI: 29%–62%). The DCR was 88% (35/40), and 25 patients (63%) remained on treatment at the time of efficacy follow-up, with a median follow-up of 6.9 months.
The activity was observed across a clinically heterogeneous, previously treated population. Patients had received a median of two prior lines of therapy; 98% had received prior osimertinib, 53% had received prior chemotherapy and/or an antibody-drug conjugate, and 53% had a history of brain metastases. Thirty-five percent of patients had concurrent T790M.
Safety Profile at Expansion Doses
Among 174 patients treated at doses of 40 mg, 50 mg and 60 mg twice daily, treatment-related dose reductions and discontinuations occurred in 9% and 3% of patients, respectively. EGFR (搜索) wild-type-associated treatment-related adverse events were primarily Grade 1. The most common treatment-related adverse event was bilirubin elevation, which was generally asymptomatic and predominantly unconjugated, consistent with UGT1A1 inhibition by BH-30643.
"These updated results provide important clinical validation of the approach we took in intentionally designing BH-30643 to address on-target EGFR (搜索) resistance, including C797S," said Geoff Oxnard, M.D., Chief Medical Officer of BlossomHill Therapeutics (搜索). "We are encouraged to see meaningful anti-tumor activity across a molecularly diverse group of patients with C797S-positive disease, including patients with concurrent T790M and those who have received multiple prior therapies, with a favorable safety profile."
Drug Design and Regulatory Status
BH-30643 is an investigational, orally bioavailable, non-covalent, macrocyclic, brain-active, mutant-selective OMNI-EGFR (搜索)™ inhibitor for the treatment of EGFR-mutant NSCLC. It was designed to overcome the limitations of currently approved EGFR inhibitors, which were discovered over a decade ago without the current understanding of the structure and protein dynamics of mutant EGFRs. In preclinical studies, BH-30643 demonstrated potent inhibitory activity across diverse EGFR mutation categories — classical 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.
The presentation follows receipt of FDA Fast Track designation for BH-30643 for the treatment of advanced or metastatic EGFR (搜索) C797S-positive NSCLC after third-generation EGFR TKI treatment.
Trial Design and Next Steps
SOLARA (NCT06706076) is a global, open-label, multicenter Phase 1/2 first-in-human study spanning more than 40 sites in 10 countries. It is assessing the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of BH-30643 in patients with EGFR (搜索)-mutant NSCLC. Phase 1 will determine the recommended Phase 2 dose as a monotherapy and in combination with chemotherapy; Phase 2 is designed to evaluate antitumor efficacy and safety in specified cohorts determined by mutation subtypes and/or treatment history at the recommended Phase 2 dose, as well as population pharmacokinetics.
Development of BH-30643 is continuing across multiple EGFR (搜索)-mutant populations, with expansion cohorts evaluating on-target resistance mutations, targeted therapy-naive patients and BH-30643 in combination with chemotherapy. BlossomHill plans to initiate a global Phase 2 study targeting EGFR C797S-positive NSCLC in Q1 2027.
"Together with the recent FDA Fast Track designation, these data strengthen our conviction in the potential of BH-30643 and support our plans to advance into a Phase 2 trial in patients with C797S-positive NSCLC in 2027," Oxnard said.
BlossomHill Therapeutics (搜索) is a clinical-stage biopharmaceutical company headquartered in San Diego, California, applying a chemistry-based approach to design small molecule medicines for cancer. Beyond BH-30643, the company is conducting clinical development of BH-30236, an investigational macrocyclic CDC-like kinase (CLK) inhibitor initially being studied in relapsed or refractory acute myeloid leukemia (搜索) and higher-risk myelodysplastic syndromes (搜索), and has a preclinical pan-KRAS (搜索) Switch-II inhibitor, BH-501284 (搜索), in its pipeline.