Background

TIS is an anti-programmed cell death protein 1 monoclonal antibody engineered to minimize FcγR binding. Primary results from this single-arm, multicenter, open-label, phase 2 study (NCT03736889) evaluating TIS in pts with MSI-H/dMMR solid tumors showed a clinically meaningful objective response rate (ORR). Here, we report updated analysis with longer follow-up.

Methods

Eligible adult participants had previously treated, locally advanced, unresectable/metastatic solid tumors with centrally confirmed MSI-H/dMMR, ≥1 measurable lesion (RECIST v1.1), and an ECOG performance status ≤1. Pts received TIS 200 mg intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was Independent Review Committee (IRC)-assessed ORR (RECIST v1.1). Secondary endpoints included overall survival (OS), IRC-assessed duration of response (DoR), progression-free survival (PFS), and disease control rate, and safety.

Results

Of 80 pts enrolled and treated in the study, 75 had measurable disease per IRC at baseline and were included in the efficacy-evaluable population. At data cutoff (Dec 5, 2022), median study follow-up was 28.9 months; minimum follow-up from last patient in to data cutoff was 28.1 months. Efficacy results are shown in the Table. ORR was 49.3%; median DoR, PFS, and OS were not reached. Treatment-emergent adverse events (TEAEs) ≥grade 3 occurred in 48 pts (60.0%); the most common was anemia, occurring in nine pts (11.3%). TEAEs leading to treatment discontinuation occurred in six pts (7.5%).

Conclusions

With a minimum of 28.1 months’ follow-up, TIS-treated pts with previously treated MSI-H/dMMR solid tumors demonstrated a higher ORR compared with previous analysis, and durable improvements in DoR, PFS, and OS, with no new safety signals. Table: 1057P

Tumor Response in the Efficacy-evaluable Population

Clinical trial identification

NCT03736889 (first posted November 9, 2018).

Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under direction of the authors, was provided by Lorena Mejias Martinez, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

J. Li: Financial Interests, Principal Investigator: BeiGene. Y. Xu: Financial Interests, Principal Investigator: BeiGene. A. Zang: Financial Interests, Principal Investigator: BeiGene. Y. Gao: Financial Interests, Principal Investigator: BeiGene. Q. Gao: Financial Interests, Principal Investigator: BeiGene. Y. Zhang: Financial Interests, Principal Investigator: BeiGene. D. Wang: Financial Interests, Principal Investigator: BeiGene. H. Jiang: Financial Interests, Principal Investigator: BeiGene. J. Ying: Financial Interests, Principal Investigator: BeiGene. C. Shi: Financial Interests, Principal Investigator: BeiGene. Y. Deng: Financial Interests, Principal Investigator: BeiGene. J. Wang: Financial Interests, Principal Investigator: BeiGene. T. Liu: Financial Interests, Principal Investigator: BeiGene. Y. Huang: Financial Interests, Principal Investigator: BeiGene. M. Shi: Financial Interests, Full or part-time Employment: BeiGene. K. Wang: Financial Interests, Full or part-time Employment: BeiGene. H. Hu: Financial Interests, Full or part-time Employment: BeiGene. L. Shen: Financial Interests, Personal, Other, Consulting fees: Mingji biopharmaceutical, Haichuang pharmaceutical, Herbour biomed; Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, BI, Sanofi, Roche, SERVIER, AZ; Financial Interests, Institutional, Funding: Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical (Shanghai), Alphamab Oncology, Yaojie Ankang (Nanjing) Technology Co., Ltd., BeiGene, Ltd., Qiyu Biotechnology (Shanghai) Co., Ltd., BriSTAR immunotech; Financial Interests, Institutional, Local PI: Merck Healthcare KGaA, Roche; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Innovent, BeiGene, Ltd., Qilu Pharmaceutical, NovaRock Biotherapeutics Limited. All other authors have declared no conflicts of interest.