Advanced Colorectal Cancer
Conditions
Keywords
MRG007, Advanced Colorectal Cancer, CDH17, ADC
Brief summary
This is a Phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of MRG007 combination therapy in patients with advanced colorectal cancer.
Interventions
DRUGMRG007
MRG007 will be administrated as specified in the protocol.
DRUG5-Fluorouracil / Leucovorin Calcium
5-Fluorouracil / Leucovorin Calcium will be administrated as specified in the protocol.
DRUGBevacizumab
Bevacizumab will be administrated as specified in the protocol.
DRUGOxaliplatin
Oxaliplatin will be administrated as specified in the protocol.
DRUGPD-1/VEGF antibody
PD-1/VEGF antibody will be administrated as specified in the protocol.
DRUGCapecitabine
Capecitabine will be administrated as specified in the protocol.
Sponsors
Lepu Biopharma Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Expected survival of ≥ 3 months. 2. Tumor tissue specimens must be provided for relevant biomarker testing. If archived tissue specimens are unavailable, a new biopsy must be performed. 3. Pathologically confirmed, unresectable locally advanced or metastatic colorectal adenocarcinoma. 4. At least one measurable lesion according to RECIST v1.1 criteria. Measurable lesions should not have received prior radiotherapy; however, measurable lesions located within a prior radiation field or after local therapy may be selected as target lesions if disease progression is confirmed. 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 6. Adequate organ function must be demonstrated. 7. Sexually active males and females of childbearing potential must agree to use highly effective contraceptive measures from the time of signing the informed consent form until 6 months after the last dose of the investigational drug. Females of childbearing potential include premenopausal females and postmenopausal females within 1 year after menopause. Females of childbearing potential must have a negative serum pregnancy test result ≤ 7 days prior to the first dose and before randomization.
Exclusion criteria
1. Trial participants with known deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H). 2. Trial participants with synchronous or multiple primary malignancies. 3. Residual toxicity ≥ Grade 2 resulting from prior anti-tumor therapy. 4. Symptomatic central nervous system (CNS) metastases and/or leptomeningeal metastases. 5. History of severe cardiovascular disease. 6. Cerebrovascular accident, pulmonary embolism, or deep vein thrombosis occurring within 3 months prior to the first dose of the investigational drug; thrombosis associated with implanted venous ports or catheters; or superficial vein thrombosis, except for patients with stable thrombosis after standard anticoagulation therapy. Prophylactic use of low-dose low-molecular-weight heparin is permitted. 7. Clinically symptomatic moderate or larger volume pleural, ascitic, or pelvic effusions requiring clinical intervention, or clinically symptomatic pericardial effusion. 8. History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of the investigational drug that has not healed following surgical treatment; risk of bowel obstruction or bowel perforation; extensive bowel resection; poorly controlled Crohn's disease, ulcerative colitis, or other gastrointestinal autoimmune or inflammatory diseases; presence of pyloric obstruction and/or persistent recurrent vomiting. 9. Active chronic hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection. 10. Hypersensitivity to any component or excipient of MRG007, or known ≥ Grade 3 hypersensitivity to other prior anti-CDH17 antibodies or other monoclonal antibodies. 11. Body weight loss ≥ 10% during the screening period. Any severe and/or uncontrolled systemic disease that, in the opinion of the investigator and the sponsor, renders the participant unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity (DLT) | From the first dose to 30 days after the last dose |
| Serious Adverse Events (SAEs) | From the first dose to 30 days after the last dose |
| Adverse Event (AE) | From the first dose to 30 days after the last dose |
| Recommended Phase 2 Dose(RP2D) and/or Maximum Tolerated Dose (MTD) | From the first dose to 30 days after the last dose |
| Objective Response Rate (ORR) | Assessments will be performed every 6 weeks (± 7 days) following the first dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration | up to 2 years | Serum Concentration of ADC, TAb, free payload will be measured. |
| Anti-Drug Antibody (ADA) | up to 2 years | The proportion of patients with positive ADA results. |
| Neutralizing antibody (NAb) | up to 2 years | The proportion of patients with positive NAb results. |
| Duration of Response (DOR) | Through study completion, an average 2 years | — |
| Disease Control Rate (DCR) | Through study completion, an average 2 years | — |
| Progression-Free Survival (PFS) | Through study completion, an average 2 years | — |
| Overall Survival (OS) | Through study completion, an average 2 years | — |
Countries
China
Contacts
CONTACTProgram Director
Outcome results
None listed