The study evaluated the investigational MTA-cooperative PRMT5 inhibitor BGB-58067 in patients with MTAP-deficient advanced tumors.

This was a first-in-human phase 1a study in patients with MTAP-deficient advanced tumors who received once-daily BGB-58067 at doses ranging from 50 mg to 800 mg. MTAP deficiency was assessed by local and/or central immunohistochemistry and/or next-generation sequencing. Endpoints included safety, antitumor activity, pharmacokinetic profile, and pharmacodynamic profile.

At data cutoff (March 20, 2026), 163 patients with a median of 2 prior lines of therapy were enrolled. The largest cohort was non-small cell lung cancer (NSCLC; N=80); 40% and 20% of patients had brain and liver metastases at baseline, respectively.

Among 163 enrolled patients, treatment-related adverse events (TRAEs) occurred in 89% and grade ≥3 TRAEs occurred in 36%. The most common TRAEs were nausea (34%), anemia (28%), fatigue (23%), and decreased appetite (23%). Five patients (3%) discontinued treatment because of TRAEs. One dose-limiting toxicity, grade 4 platelet count decreased, was reported at the 800 mg dose level.

With a median treatment follow-up of 3.6 months, the unconfirmed ORR across evaluable non-central nervous system tumor types was 24.6% (31/126), and the DCR was 73.0% (92/126). Among 41 efficacy-evaluable patients with NSCLC treated at the recommended phase 2 dose ranges, the unconfirmed ORR was 31.7% and the DCR was 68.3%. Responses were observed across histological subtypes and in patients with baseline brain metastases, with evidence of intracranial response.

An approximately linear and dose-proportional increase in steady-state exposure of BGB-58067 across the 50 mg to 800 mg dose range was reported. Target engagement was confirmed by symmetric dimethylarginine reduction in tumor tissue and blood.