A phase Ia first-in-human study of BPB-101, a novel trifunctional antibody targeting the GARP/TGF-β complex and PD-L1, in patients with locally advanced or metastatic solid tumors.
Yuxiang Ma, Yufeng Guo, Shuang Deng et al.
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In 30 seconds
This phase Ia, multicenter, first-in-human dose-escalation study evaluated BPB-101, a trifunctional antibody targeting the GARP/TGF-β complex and PD-L1, in previously treated patients with advanced or metastatic solid tumors. Among 19 enrolled patients, treatment-related adverse events occurred in 78.9%; two patients (10.5%) had grade ≥ 3 events, both anemia. No dose-limiting toxicities or treatment-related deaths occurred, and the maximum tolerated dose was not reached. In the 17-patient efficacy set, the immune objective response rate was 5.9% (95% CI, 0.1-28.7). The 1200 mg and 1800 mg every-three-week doses were selected for further evaluation.
Key findings
- Treatment-related adverse events occurred in 15 of 19 patients (78.9%); grade ≥ 3 events occurred in two (10.5%), both anemia.
- No dose-limiting toxicities or treatment-related deaths occurred, and the maximum tolerated dose was not reached.
- Among 17 patients in the efficacy analysis set, the immune objective response rate was 5.9% (95% CI, 0.1-28.7), and the immune disease control rate was 47.1% (95% CI, 23.0-72.2).
- Peripheral assessments showed high receptor occupancy and reduced circulating TGF-β1 in the 1200 mg and 1800 mg cohorts.
Why it matters
The study provides early human safety, pharmacodynamic, and antitumor activity data for an antibody designed to target both GARP/TGF-β and PD-L1. The findings support continued investigation, while the low observed response rate and wide confidence interval underscore that efficacy remains uncertain at this early stage.
What to keep in mind
This was a phase Ia dose-escalation study with 19 patients; the efficacy analysis included 17, limiting the precision and generalisability of preliminary activity estimates.