A Study Comparing BL-M07D1 With Physician's Choice Therapy in Patients With HER2 IHC3+ Advanced Colorectal Cancer Who Failed Prior Treatment With Oxaliplatin, Fluorouracil and Irinotecan

Official title

A Phase III Randomized Controlled Clinical Study Comparing BL-M07D1 With Physician's Choice Therapy in Patients With HER2 IHC3+ Advanced Colorectal Cancer Who Failed Prior Treatment With Oxaliplatin, Fluorouracil and Irinotecan

Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study designed to evaluate the efficacy and safety of BL-M07D1 in patients with advanced colorectal cancer who have HER2 IHC3+ and have failed prior treatment with oxaliplatin, fluorouracil and irinotecan.

Interventions

• Drug BL-M07D1
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Regorafenib
  Oral administration, once daily (QD) for a cycle of 4 weeks.
• Drug Fruquintinib
  Oral administration, once daily (QD) for a cycle of 4 weeks.
• Drug TAS-102
  Oral administration, twice daily for a cycle of 4 weeks.

Primary outcome measures

• BICR-assessed Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]

Secondary outcome measures (12)

• Overall Survival (OS) [Time frame: Up to approximately 24 months]
• Investigator-assessed Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Treatment Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• T1/2 [Time frame: Up to approximately 24 months]
• AUC0-t [Time frame: Up to approximately 24 months]
• CL (Clearance) [Time frame: Up to approximately 24 months]
• Ctrough [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• Participants must be ≥18 years and ≤75 years of age on the day of signing the informed consent form;
• Expected survival time ≥3 months;
• Patients with histologically or cytologically confirmed metastatic colorectal cancer;
• Prior failure of standard therapy;
• Patients suitable for receiving the control regimen treatment;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
• Organ function levels must meet the requirements;
• For premenopausal women of childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the result must exclude pregnancy; they must be non-lactating; all enrolled participants must use adequate barrier contraception throughout the entire treatment period and for 7 months after the end of treatment.

Exclusion criteria

• Have undergone surgical treatment, radical radiotherapy, chemotherapy, immunotherapy, etc. within 4 weeks before the first dose;
• Have previously received ADC drug therapy using camptothecin derivatives as toxins, or have previously received HER2-ADC drug therapy;
• History of severe cardiovascular or cerebrovascular disease within half a year before screening;
• Concurrent pulmonary disease resulting in severely impaired lung function;
• Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
• Diagnosed with active malignancy within 3 years before study randomization;
• Any thrombotic event within 6 months before randomization;
• Hypertension inadequately controlled by two antihypertensive agents;
• Poorly controlled blood glucose;
• History of interstitial lung disease (ILD)/interstitial pneumonia, current ILD/interstitial pneumonia, etc.;
• Trial participants with active central nervous system metastases;
• Patients with a history of allergy to recombinant humanized antibodies or allergy to any excipient of BL-M07D1;
• History of autologous or allogeneic stem cell transplantation or organ transplantation;
• Positive for human immunodeficiency virus antibody, active hepatitis B virus infection, or hepatitis C virus infection;
• Severe infection occurring within 4 weeks before the first use of the study drug;
• Patients with massive serous cavity effusion, or symptomatic serous cavity effusion, or poorly controlled serous cavity effusion;
• Receiving long-term systemic corticosteroid therapy at a dose >10 mg/day prednisone within 14 days before randomization, etc.;
• History of severe neurological or psychiatric disease;
• Severe and non-healing wounds, ulcers, or fractures occurring within 4 weeks before signing informed consent;
• Clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing informed consent;
• Crohn's disease, ulcerative colitis, or chronic diarrhea, etc.;
• Received other unapproved clinical study drugs or treatments within 4 weeks before study randomization;
• Patients planning to receive or having received live vaccines within 28 days before the first dose;
• Imaging findings indicate that the tumor has invaded or encased major blood vessels in the abdomen, chest, neck, or pharynx;
• Presence of other serious physical conditions, abnormal laboratory findings, or poor compliance, etc., that may increase the risk of participating in the study, interfere with the study results, or are considered by the investigator as 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

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• The First Hospital of China Medical University — Shenyang
• ZhongShan Hospital Fudan University — Shanghai

Identifiers

NCT: NCT07730489 · BL-M07D1-310

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗