348MO - A phase Ib/II study to assess the safety and efficacy of PM8002/BNT327 in combination with nab-paclitaxel for first-line treatment of locally advanced or metastatic triple-negative breast cancer

Background

PD-L1 and VEGF play important roles in immune evasion and tumoral angiogenesis promoting cancer growth and metastasis. PM8002/BNT327 is a bispecific antibody targeting PD-L1 and VEGF-A developed for the treatment of solid tumors. We conducted a Phase Ib/II study of PM8002 in combination with nab-paclitaxel in pts with locally advanced or metastatic triple-negative breast cancer (la/mTNBC).

Methods

Pts with previously untreated la/mTNBC were enrolled to assess the safety and efficacy of PM8002 in combination with nab-paclitaxel. All pts received PM8002 and nab-paclitaxel. Primary objectives were safety and objective response rate (ORR) per RECIST v1.1 by investigator assessment, with progression free survival (PFS) and overall survival (OS) as the secondary objectives.

Results

As of Mar 15 2024, 42 pts were enrolled. The median duration of drug exposure was 10 months. 13 pts were still on treatment. The median PFS was 13.3 months for the ITT population. The ORR was 78.6%, including 1 complete response and 32 partial responses (PR), the confirmed ORR(cORR) was 73.8% with the disease control rate of 95.2%. Among the 42 pts treated, 38 pts had available PD-L1 expression results. cORR was 76.9% in 13 pts with PD-L1 combined positive scores (CPS) < 1 and 72.0% in 25 pts with PD-L1 CPS ≥1. All 9 pts with PD-L1 CPS ≥10 achieved PR. All pts experienced treatment-related adverse events (TRAEs), 54.8% were Grade 3 or 4 and, no Grade 5 TRAEs was observed. The most common TRAEs included neutropenia, leukocytopenia, anemia, proteinuria, alopecia and epistaxis. 35.7% of pts experienced immune-related adverse events (irAEs), 9.5% were Grade 3 or 4, including hyperthyroidism, hypothyroidism and rash. The most common AEs typically associated with VEGF inhibition were hypertension and proteinuria which were mostly Grade 1-2.

Conclusions

PM8002 combined with nab-paclitaxel showed encouraging antitumor activity and acceptable safety as first-line therapy for locally advanced and metastatic TNBC. This Phase II study is still ongoing, and a phase III study has been approved to be conducted in China based on these results.

Clinical trial identification

NCT05918133.

Editorial acknowledgement

We would like to thank the pts and their families for their contribution to this trial.

Legal entity responsible for the study

Biotheus Inc.

Funding

Biotheus Inc.

Disclosure

J. Wu: Financial Interests, Personal, Advisory Role: Astrazeneca; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Licencing Fees or royalty for IP: Huodian. All other authors have declared no conflicts of interest.