CRC, Colorectal Cancer
Conditions
Keywords
HDM2017, CRC
Brief summary
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.
Interventions
DRUGHDM2017
Administered with continuing until protocol-specified criteria for treatment discontinuation are met
DRUGBevacizumab
administered with continuing until protocol-specified criteria for treatment discontinuation are met
DRUGOxaliplatin
administered with continuing until protocol-specified criteria for treatment discontinuation are met
DRUGFluorouracil
administered with continuing until protocol-specified criteria for treatment discontinuation are met
DRUGCapecitabine
administered with continuing until protocol-specified criteria for treatment discontinuation are met
DRUGLeucovorin
administered with dosing continuing until protocol-specified criteria for treatment discontinuation are met
Sponsors
Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 30 days after the last dose of IMP | The MTD will be determined using DLTs |
| Recommended Phase 2 Dose (RP2D) | 30 days after the last dose of IMP | The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data |
| Type, incidence and severity of Adverse Events | 30 days after the last dose of IMP | Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v6.0 |
| Objective Response Rate (ORR) | From date of first-dosing until the date of first documented progression or date of 30 days after the last dose of IMP, whichever came first, assessed up to about 12 months | ORR is defined as the proportion of subjects with BOR response of CR or PR (based on RECIST Version 1.1). |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate (DCR) | 30 days after the last dose of IMP |
| Duration of Response (DoR) | From date of confirm ORR until the date of first documented progression, assessed up to about 36 months |
| Progression Free Survival (PFS) | From date of first-dosing/randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to about 36 months |
| Overall survival (OS) | From date of first-dosing/randomization until the end of the trail or date of death from any cause, whichever came first, assessed up to about 48 months |
| Incidence of anti-drug antibody (ADA) | 30 days after the last dose of IMP |
Countries
China
Contacts
CONTACTLin Shen
Outcome results
None listed