59O - A first-in-human, phase I study of BPI-371153, a novel small-molecule PD-L1 inhibitor, in advanced solid tumors or recurrent/refractory (r/r) lymphoma

Background

BPI-371153, a novel, oral small molecule, disrupts PD-1/PD-L1 interaction by inducing PD-L1 dimerization and internalization. Here we present the results from ongoing phase I study.

Methods

Eligible patients (pts) had an ECOG PS 0-1 and disease progression after available treatment or were ineligible for/without access to standard of care. Study started with dose escalation (100-1600 mg QD) in advanced solid tumors or r/r lymphoma, followed by dose expansion at 2 dose levels (800 mg and 1200 mg QD) which included advanced NSCLC, extensive-stage SCLC, r/r lymphoma, and other advanced solid tumors. Primary endpoints are safety, tolerability, and pharmacokinetics.

Results

As of April 26, 2024, 20 pts had received at least one dose of BPI-371153, including 16 solid tumors (11 NSCLC) and 4 lymphomas. The median age was 58 years (range, 33-76), and 70% of pts received ≥ 2 prior lines of systematic treatment including ICIs. No dose-limiting toxicity was reported and the maximum tolerated dose was not reached. In ≤1200 mg dose cohort, the TRAEs were 88% and the ≥ grade 3 TRAEs were 6%, with the most common TRAEs being diarrhea (65%), vomiting (18%), abdominal pain (18%), and elevated ALT (18%). No death was observed at all dose levels. Pharmacokinetic evaluation showed near dose-proportional systemic exposure with a mean half-life of 20.8-26.2 h, supporting QD dosing. The receptor occupancies of PD-L1 on monocytes in peripheral blood were sufficient and similar in ≥ 600 mg dose groups. Dose levels ≥ 600 mg QD showed anti-cancer activity. Shrinkage was seen in 7 patients, including 3 received previous ICIs, and the longest ongoing shrinkage was > 12 months. Tumor response was observed in 4 pts, including one CR in lung adenocarcinoma, and 3 PR in NSCLC or Hodgkin lymphoma. Among responsive pts, 3 had positive PD-L1 expression, and one had high TMB.

Conclusions

BPI-371153 presented manageable safety profile, favorable pharmacokinetics, and encouraging anti-cancer activities in advanced solid tumors or r/r lymphoma.

Clinical trial identification

NCT05341557.

Editorial acknowledgement

Legal entity responsible for the study

Betta Pharmaceuticals Co. Ltd.

Funding

Betta Pharmaceuticals Co. Ltd.

Disclosure

X. Du, X. Liu, Z. Shen, P. Li, L. Ding: Financial Interests, Personal, Full or part-time Employment: Betta Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.