A Study of MRG007 Combination Therapy for Advanced Colorectal Cancer

Official title

Phase Ib/II Clinical Study of the Safety, Tolerability, Pharmacokinetics, and Efficacy of MRG007 Combination Therapy in Patients With Advanced Colorectal Cancer

Overview

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

• Drug MRG007
  MRG007 will be administrated as specified in the protocol.
• Drug 5-Fluorouracil / Leucovorin Calcium
  5-Fluorouracil / Leucovorin Calcium will be administrated as specified in the protocol.
• Drug Bevacizumab
  Bevacizumab will be administrated as specified in the protocol.
• Drug Oxaliplatin
  Oxaliplatin will be administrated as specified in the protocol.
• Drug PD-1/VEGF antibody
  PD-1/VEGF antibody will be administrated as specified in the protocol.
• Drug Capecitabine
  Capecitabine will be administrated as specified in the protocol.

Primary outcome measures

• Dose Limiting Toxicity (DLT) [Time frame: From the first dose to 30 days after the last dose]
• Serious Adverse Events (SAEs) [Time frame: From the first dose to 30 days after the last dose]
• Adverse Event (AE) [Time frame: From the first dose to 30 days after the last dose]
• Recommended Phase 2 Dose(RP2D) and/or Maximum Tolerated Dose (MTD) [Time frame: From the first dose to 30 days after the last dose]
• Objective Response Rate (ORR) [Time frame: Assessments will be performed every 6 weeks (± 7 days) following the first dose.]

Secondary outcome measures (7)

• Serum Concentration [Time frame: up to 2 years]
• Anti-Drug Antibody (ADA) [Time frame: up to 2 years]
• Neutralizing antibody (NAb) [Time frame: up to 2 years]
• Duration of Response (DOR) [Time frame: Through study completion, an average 2 years]
• Disease Control Rate (DCR) [Time frame: Through study completion, an average 2 years]
• Progression-Free Survival (PFS) [Time frame: Through study completion, an average 2 years]
• Overall Survival (OS) [Time frame: Through study completion, an average 2 years]

Eligibility criteria

Inclusion criteria

• Expected survival of ≥ 3 months.
• Tumor tissue specimens must be provided for relevant biomarker testing. If archived tissue specimens are unavailable, a new biopsy must be performed.
• Pathologically confirmed, unresectable locally advanced or metastatic colorectal adenocarcinoma.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Adequate organ function must be demonstrated.
• 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

• Trial participants with known deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H).
• Trial participants with synchronous or multiple primary malignancies.
• Residual toxicity ≥ Grade 2 resulting from prior anti-tumor therapy.
• Symptomatic central nervous system (CNS) metastases and/or leptomeningeal metastases.
• History of severe cardiovascular disease.
• 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.
• Clinically symptomatic moderate or larger volume pleural, ascitic, or pelvic effusions requiring clinical intervention, or clinically symptomatic pericardial effusion.
• 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.
• Active chronic hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• Hypersensitivity to any component or excipient of MRG007, or known ≥ Grade 3 hypersensitivity to other prior anti-CDH17 antibodies or other monoclonal antibodies.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University cancer Hospital — Beijing

Identifiers

NCT: NCT07737600 · MRG007-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗