Reference Detail

Ref Type

Abstract

PMID

Authors

Yiwen Chen, Xinjun Liang, Yu Chen, Hui Wang, Yuping Sun, Yueyin Pan, Jian Zhang, Jiuwei Cui, Qian Chu, Guang-Hai Dai, Liang Kang, Huiwen Ma, Jianzhen Shan, Weijia Fang, Yu-Long Zheng, Nong Xu, Weiqin Jiang, Cong Wei, Li Zhao, and Tingbo Liang

Title

First-in-class PD-1/IL-2 bispecific antibody fusion protein IBI363 in patients with advanced colorectal cancer: Safety and efficacy results from a phase I study.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	42	no. 16_suppl	May 29, 2024	3593	J Clin Oncol

URL

https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3593

Abstract Text

Background: The prognosis of advanced colorectal cancer (CRC) is poor with limited treatment options available. IBI363 is a PD-1/IL-2α-bias bispecific antibody that specifically activate PD-1(+)CD25(+) tumor specific T cells while sparing PD-1(-)CD25(-) bystander T cells, and activate peripheral regulatory T cells to protect the body from autoimmunity. Herein, we report the safety and efficacy of IBI363 in patients (pts) with advanced CRC in a phase I study. Methods: Eligible pts with locally advanced or metastatic CRC who failed or intolerant to standard treatment were enrolled and received IBI363 intravenously at dose levels ranging from 100 ug/kg to 3 mg/kg every week (QW), every two weeks (Q2W) or every three weeks (Q3W). The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), etc. per RECIST v1.1. Results: As of December 22, 2023, a total of 68 pts (males: 55.9%, median age: 55.5 years, ECOG PS 1: 50.0%, liver metastasis: 61.8%; previous treatment ≥3 lines: 76.5%; previous immunotherapy: 27.9%) were recruited and received IBI363 treatment including 24 pts at 600 ug/kg Q2W and 20 pts at 1 mg/kg Q2W. Microsatellite stable (MSS)/proficient mismatch repair (pMMR) was presented in 57 (83.8%) pts and microsatellite status of the remaining 11 (16.2%) pts were unknown. Median follow up time was 5.3 months (95%CI: 4.4-6.9). Treatment emergent adverse events (TEAEs) were reported in 65 (95.6%) pts including grade ≥3 TEAEs in 22 (32.4%) pts. Common TEAEs (≥20%) were arthralgia (35.3%), anemia (32.4%), pyrexia (22.1%) and hypoalbuminemia (20.6%). Treatment related adverse events (TRAEs) were reported in 62 (91.2%) pts including grade ≥3 TRAEs in 16 (23.5%) pts. Immune related adverse events (irAEs) were reported in 22 (32.4%) pts including grade ≥3 irAEs in 4 (5.9%) pts. Serious TRAE were reported in 12 (17.6%) pts. TRAEs leading to treatment interruption and discontinuation were reported in 25 (36.8%) and 2 (2.9%) pts. No TRAE leading to death was reported. Pts with at least 1 post-baseline tumor assessment were included in efficacy evaluable set. In all evaluable pts (n=63), overall ORR was 12.7% (95%CI: 5.6-23.5). In pts with liver metastasis (n=38), ORR was 13.2% (95%CI: 4.4-28.1). In pts with PD-L1 CPS ≥1 (n=13), ORR was 30.8% (95%CI: 9.1-61.4), and DCR was 76.9% (95%CI: 46.2-95.0). The median DoR was not reached. A prospective cohort of CRC pts with PD-L1 CPS ≥1 has been initiated. Further details and data will be updated at the meeting. Conclusions: IBI363 showed acceptable tolerability and manageable safety profiles in pts with advanced CRC. Preliminary efficacy of IBI363 was observed, particularly in pts with PD-L1 CPS ≥1. Clinical trial information: NCT05460767.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	colorectal cancer	predicted - sensitive	IBI363	Phase I	Actionable	In a Phase I trial, IBI363 treatment demonstrated safety in patients with advanced or metastatic CD274 (PD-L1)-positive (CPS>=1) colorectal cancer who had failed on or were intolerant to standard therapy (n=13) and resulted in an objective response rate of 30.8% and disease control rate of 76.9% (J Clin Oncol 42, 2024 (suppl 16; abstr 2504); NCT05460767).	detail...