643P - A phase Ib/IIa study to assess the safety, tolerability, pharmacokinetics, and antitumor activity of YYB101, hepatocyte growth factor neutralizing humanized monoclonal antibody, in combination with irinotecan in metastatic or recurrent colorectal cancer patients (NOV110501-201)

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.