Colorectal Cancer
Conditions
Brief summary
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
DRUGBL-M07D1
Administration by intravenous infusion for a cycle of 3 weeks.
DRUGRegorafenib
Oral administration, once daily (QD) for a cycle of 4 weeks.
DRUGFruquintinib
Oral administration, once daily (QD) for a cycle of 4 weeks.
DRUGTAS-102
Oral administration, twice daily for a cycle of 4 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form and comply with the protocol requirements; 2. Participants must be ≥18 years and ≤75 years of age on the day of signing the informed consent form; 3. Expected survival time ≥3 months; 4. Patients with histologically or cytologically confirmed metastatic colorectal cancer; 5. Prior failure of standard therapy; 6. Patients suitable for receiving the control regimen treatment; 7. Must have at least one measurable lesion as defined by RECIST v1.1; 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 9. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0; 10. Organ function levels must meet the requirements; 11. 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
1. Have undergone surgical treatment, radical radiotherapy, chemotherapy, immunotherapy, etc. within 4 weeks before the first dose; 2. Have previously received ADC drug therapy using camptothecin derivatives as toxins, or have previously received HER2-ADC drug therapy; 3. History of severe cardiovascular or cerebrovascular disease within half a year before screening; 4. Concurrent pulmonary disease resulting in severely impaired lung function; 5. Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias; 6. Diagnosed with active malignancy within 3 years before study randomization; 7. Any thrombotic event within 6 months before randomization; 8. Hypertension inadequately controlled by two antihypertensive agents; 9. Poorly controlled blood glucose; 10. History of interstitial lung disease (ILD)/interstitial pneumonia, current ILD/interstitial pneumonia, etc.; 11. Trial participants with active central nervous system metastases; 12. Patients with a history of allergy to recombinant humanized antibodies or allergy to any excipient of BL-M07D1; 13. History of autologous or allogeneic stem cell transplantation or organ transplantation; 14. Positive for human immunodeficiency virus antibody, active hepatitis B virus infection, or hepatitis C virus infection; 15. Severe infection occurring within 4 weeks before the first use of the study drug; 16. Patients with massive serous cavity effusion, or symptomatic serous cavity effusion, or poorly controlled serous cavity effusion; 17. Receiving long-term systemic corticosteroid therapy at a dose \>10 mg/day prednisone within 14 days before randomization, etc.; 18. History of severe neurological or psychiatric disease; 19. Severe and non-healing wounds, ulcers, or fractures occurring within 4 weeks before signing informed consent; 20. Clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing informed consent; 21. Crohn's disease, ulcerative colitis, or chronic diarrhea, etc.; 22. Received other unapproved clinical study drugs or treatments within 4 weeks before study randomization; 23. Patients planning to receive or having received live vaccines within 28 days before the first dose; 24. Imaging findings indicate that the tumor has invaded or encased major blood vessels in the abdomen, chest, neck, or pharynx; 25. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BICR-assessed Progression-free Survival (PFS) | Up to approximately 24 months | Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to approximately 24 months | Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death. |
| Overall Survival (OS) | Up to approximately 24 months | Overall survival (OS) is defined as the time between the day the subject is randomized and the subject's death. |
| Investigator-assessed Progression-free Survival (PFS) | Up to approximately 24 months | Investigator-assessed progression-free survival (PFS) per RECIST v1.1 is defined as the time from treatment initiation until the first documented disease progression according to RECIST v1.1 criteria, or death from any cause, whichever occurs first, as determined by the local treating investigator. |
| Objective Response Rate (ORR) | Up to approximately 24 months | Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS). |
| Treatment Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M07D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M07D1. |
| Cmax | Up to approximately 24 months | Cmax is defined as the maximum observed drug concentration in plasma after administration. |
| Tmax | Up to approximately 24 months | Tmax is defined as the time required to reach the maximum drug concentration in plasma following drug administration. |
| T1/2 | Up to approximately 24 months | T1/2 is defined as the time required for the plasma concentration of a drug to decrease by 50% during the elimination phase. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | Clearance (CL) is the volume of plasma from which a drug is completely removed per unit time. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration prior to the next dose will be administered. |
| Anti-drug Antibody (ADA) | Up to approximately 24 months | Anti-drug Antibody (ADA) refers to endogenous antibodies generated in subjects that specifically bind to the investigational drug. |
| Disease Control Rate (DCR) | Up to approximately 24 months | Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria. |
| Neutralizing Antibody(NAb) | Up to approximately 24 months | Frequency of anti-BL-M07D1 neutralizing antibodies will be investigated. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed