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
6 affiliations
- 1Department of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Centre, Guangdong Provincial Clinical Research Centre for Cancer, Guangzhou, China
- 2Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China
- 3Phase I Clinical Research Center, Henan Cancer Hospital, Zhengzhou, China
- 4Department Five of Gynecological Oncology, Hunan Cancer Hospital, Changsha, China
- 5Betta Pharmaceuticals Co., Ltd, Hangzhou, China
- 6Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Centre, Guangdong Provincial Clinical Research Centre for Cancer, Guangzhou, China
Abstract
Background: BPB-101 is a first-in-class, humanized trifunctional bispecific IgG1 antibody targeting the GARP/TGF-β complex, active TGF-β, and PD-L1, with preclinical evidence of immunomodulatory and antitumor activity. This phase Ia study aimed to assess the safety, tolerability, pharmacology, and preliminary antitumor activity of BPB-101.
Methods: A modified accelerated titration design (6, 20, and 60 mg) was followed by a 3 + 3 escalation (200–1800 mg), with intravenous dosing every 3 weeks (Q3W). Eligible patients with advanced or metastatic solid tumors who had received prior standard systemic treatment were enrolled. The primary objectives were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory objectives included pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity.
Results: At the data cutoff of January 26, 2025, 19 patients with advanced tumors were enrolled. Treatment-related adverse events (TRAEs) occurred in 15 patients (78.9%), with the most common TRAEs being infusion-related reactions (26.3%), anemia (26.3%), and asthenia (21.1%). Grade ≥ 3 TRAEs were reported in two patients (10.5%), both of whom had anemia, with one patient each in the 400 mg and 800 mg groups. No DLTs or treatment-related deaths occurred, and the MTD was not reached. One patient in the 1800 mg cohort permanently discontinued treatment due to an immune-related TRAE (myalgia). BPB-101 exposure increased approximately dose-proportionately at doses ≥ 800 mg. Peripheral PD assessments showed high receptor occupancy (RO) and reductions in circulating TGF-β1 levels in the 1200 mg and 1800 mg cohorts. The 1200 mg and 1800 mg Q3W doses were selected as RP2Ds for further evaluation. Among 17 patients in the efficacy analysis set (EAS), one achieved confirmed immune partial response (iPR) and seven achieved immune stable disease (iSD). The overall immune objective response rate (iORR) was 5.9% (95% CI, 0.1–28.7), and the immune disease control rate (iDCR) was 47.1% (95% CI, 23.0–72.2).
Conclusions: BPB-101 showed a manageable safety profile, peripheral PD activity, and preliminary antitumor activity, supporting further evaluation in expansion cohorts.
Trial registration: This study was registered with ClinicalTrials.gov (NCT05869240); part of the study was reported at ESMO ASIA 2025 as an oral presentation. Abstract No: 158O.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13045-026-01867-7.
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BibTeX
@article{ma2026phase,
title = {{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}},
author = {Yuxiang Ma and Yufeng Guo and Shuang Deng and Haitao Lan and Suxia Luo and Keqiang Zhang and Qingqing Hu and Tao Fu and Pengxiang Wu and Qiuyue Cao and Luyang Zhao and Li Mao and Lieming Ding and Yan Huang and Yuanyuan Zhao and Yang Zhang and Jinhui Xue and Li Zhang and Hongyun Zhao},
journal = {Journal of Hematology \& Oncology},
year = {2026},
month = nov,
doi = {10.1186/s13045-026-01867-7},
url = {https://doi.org/10.1186/s13045-026-01867-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Yuxiang Ma
AU - Yufeng Guo
AU - Shuang Deng
AU - Haitao Lan
AU - Suxia Luo
AU - Keqiang Zhang
AU - Qingqing Hu
AU - Tao Fu
AU - Pengxiang Wu
AU - Qiuyue Cao
AU - Luyang Zhao
AU - Li Mao
AU - Lieming Ding
AU - Yan Huang
AU - Yuanyuan Zhao
AU - Yang Zhang
AU - Jinhui Xue
AU - Li Zhang
AU - Hongyun Zhao
PY - 2026
DA - 2026/11/03
JO - Journal of Hematology & Oncology
DO - 10.1186/s13045-026-01867-7
UR - https://doi.org/10.1186/s13045-026-01867-7
AB - Background: BPB-101 is a first-in-class, humanized trifunctional bispecific IgG1 antibody targeting the GARP/TGF-β complex, active TGF-β, and PD-L1, with preclinical evidence of immunomodulatory and antitumor activity. This phase Ia study aimed to assess the safety, tolerability, pharmacology, and preliminary antitumor activity of BPB-101. Methods: A modified accelerated titration design (6, 20, and 60 mg) was followed by a 3 + 3 escalation (200–1800 mg), with intravenous dosing every 3 weeks (Q3W). Eligible patients with advanced or metastatic solid tumors who had received prior standard systemic treatment were enrolled. The primary objectives were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory objectives included pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity. Results: At the data cutoff of January 26, 2025, 19 patients with advanced tumors were enrolled. Treatment-related adverse events (TRAEs) occurred in 15 patients (78.9%), with the most common TRAEs being infusion-related reactions (26.3%), anemia (26.3%), and asthenia (21.1%). Grade ≥ 3 TRAEs were reported in two patients (10.5%), both of whom had anemia, with one patient each in the 400 mg and 800 mg groups. No DLTs or treatment-related deaths occurred, and the MTD was not reached. One patient in the 1800 mg cohort permanently discontinued treatment due to an immune-related TRAE (myalgia). BPB-101 exposure increased approximately dose-proportionately at doses ≥ 800 mg. Peripheral PD assessments showed high receptor occupancy (RO) and reductions in circulating TGF-β1 levels in the 1200 mg and 1800 mg cohorts. The 1200 mg and 1800 mg Q3W doses were selected as RP2Ds for further evaluation. Among 17 patients in the efficacy analysis set (EAS), one achieved confirmed immune partial response (iPR) and seven achieved immune stable disease (iSD). The overall immune objective response rate (iORR) was 5.9% (95% CI, 0.1–28.7), and the immune disease control rate (iDCR) was 47.1% (95% CI, 23.0–72.2). Conclusions: BPB-101 showed a manageable safety profile, peripheral PD activity, and preliminary antitumor activity, supporting further evaluation in expansion cohorts. Trial registration: This study was registered with ClinicalTrials.gov (NCT05869240); part of the study was reported at ESMO ASIA 2025 as an oral presentation. Abstract No: 158O. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13045-026-01867-7.
SN - 1756-8722
ER -