Abstract 643P
Background
The hepatocyte growth factor (HGF)/MET pathway is implicated in tumorigenesis and treatment resistance of colorectal cancer (CRC). This report presents final results of a multi-center phase Ib/IIa study investigating biweekly YYB101, an anti-HGF monoclonal antibody, combined with irinotecan in refractory metastatic/recurrent CRC.
Methods
Eligible patients had metastatic/recurrent CRC with disease progression <6 months from the last irinotecan dose. phase Ib determined the recommended phase II dose (RP2D) of YYB101 with irinotecan (150 mg/m2), starting at 20 mg/kg, focusing on dose-limiting toxicities (DLT) incidence. Phase IIa assessed objective response rate (ORR) as the primary endpoint, with secondary endpoints including progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety, and pharmacokinetics. Archival tissue specimens and serial blood samples were collected for exploratory analysis.
Results
Thirty-five patients, aged 42-73 (median: 56), were enrolled. All had received ≥3 prior therapy lines (42.9% ≥4 lines). No DLTs were reported in phase Ib, with 20 mg/kg YYB101 selected as RP2D. In phase IIa, ORR was 5.7% (2/35) [95% confidence interval (CI), 0.70–19.16], and DCR was 82.9% (95% CI, 66.4–99.4). Median PFS was 4.80 months (95% CI, 3.15-8.84), and median OS was 14.9 months (95% CI, 9.30–not reached). Adverse events were generally manageable, mostly grades 1-2. During the COVID-19 pandemic, 54.3% of patients skipped one or two YYB101 doses but maintained serum concentrations above the predicted minimum effective concentration (100 μg/ml).
Conclusions
The YYB101 and irinotecan combination showed modest efficacy and tolerable adverse events in refractory metastatic/recurrent CRC. Ongoing biomarker analyses aim to identify genomic and transcriptomic variables associated with long-term disease control.
Clinical trial identification
NCT04368507.
Editorial acknowledgement
Legal entity responsible for the study
National OncoVenture, National Cancer Center, Goyang, Korea; CellabMED Inc, Seoul, Korea.
Funding
National OncoVenture and National Cancer Center, funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HI11C1191); CellabMED Inc, Seoul, Korea.
Disclosure
Y. Cha: Financial Interests, Personal, Advisory Board: IMBdx, Inc.; Financial Interests, Personal, Invited Speaker: Roche, MSD Korea; Financial Interests, Personal, Other, Consulting fee: Ono Pharmaceutical, GC Genome Corporation, Boryung Pharmaceutical, Interpark Bioconvergence Corp.; Non-Financial Interests, Principal Investigator: CellabMED Co., Ltd.; Non-Financial Interests, Advisory Role: National OncoVenture, Goyang, Korea; Non-Financial Interests, Member: Korean Society of Medical Oncology, SWOG, Korean Society of Medical Oncology, Korean Cancer Association, American Association for Cancer Research, American Society of Clinical Oncology. S. Song, J.Y. Choi: Financial Interests, Personal, Full or part-time Employment: CellabMED Co., Ltd. Y.W. Park: Financial Interests, Personal, Ownership Interest: Avelos Therapeutics. All other authors have declared no conflicts of interest.
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