A Study of HDM2017 Combination Therapy in Advanced Colorectal Cancer

A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HDM2017 Combination Therapy in Participants With Advanced Colorectal Cancer

This is a multicenter, open-label, dose-escalation/dose-expansion, Phase Ib/II study to evaluate the safety, tolerability, PK characteristics, and preliminary anti-tumor efficacy of HDM2017 combination therapy in participants with advanced CRC. The study is divided into two periods: dose escalation (Phase Ib) and dose expansion (Phase II). Phase Ib of this study is a dose-finding study of different HDM2017 combination therapies. The Phase II study will be conducted at a dose determined to be safe and potentially effective in Phase Ib.

Inclusion Criteria:

1. Participants must voluntarily participate in this study and sign the written ICF after being fully informed.
2. Male or female participants aged 18 to 75 years (inclusive).
3. Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic CRC.
4. Able to provide fresh or archived tumor tissue samples during the screening period.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
6. Life expectancy ≥ 3 months.
7. Participants must have at least one measurable lesion according to RECIST v1.1.
8. Laboratory test results at the screening period must indicate that the participant has adequate organ function.
9. Women of childbearing potential (WOCBP) must agree to use a reasonable method of contraception from the time of signing the ICF until 7 months after the last dose; and must have a negative serum human chorionic gonadotropin (HCG) test within 7 days before the first dose. Male participants must agree to use adequate contraception from the first dose until 7 months after the last dose.
10. Participants must be willing and able to complete regular visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Prior or current treatment with topoisomerase I (TOP I) inhibitor drugs.
2. Prior or current treatment targeting CDH17.
3. Presence of other malignant tumor, other than the tumor being treated in this study.
4. AEs from prior therapy that have not resolved to Grade 1 or baseline status before prior therapy.
5. Active central nervous system (CNS) metastasis; metastases to meninges or brainstem metastasis; presence of spinal cord compression.
6. Presence of diseases that may affect the efficacy and safety of the IMP.
7. Known or suspected allergic reaction or contraindication to any component of the IMP or its analogues.
8. Pregnant or lactating women, or those who plan to become pregnant during the study.