A Study of SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody in Patients With Locally Advanced or Metastatic Esophageal Cancer, Gastric Cancer, Colorectal Cancer and Other Gastrointestinal Tumors

Sichuan Baili Pharmaceutical

Status and phase: Enrolling; Phase 2

Conditions: Gastric Cancer; Esophageal Cancer; Colorectal Cancer

Treatments: Drug: BL-B01D1; Drug: PD-1 Monoclonal Antibody; Drug: SI-B003

Study type: Interventional

Funder types: Industry

Identifiers

NCT06008054

BL-B01D1-SI-B003-201-05

Details and patient eligibility

About

This phase II study is a clinical study to explore the efficacy and safety of SI-B003 Monotherapy, BL-B01D1+SI-B003 Combination Therapy and BL-B01D1+PD-1 Monoclonal Antibody in patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors.

Full description

To explore the efficacy, safety and tolerability of SI-B003 Monotherapy, BL-B01D1+SI-B003 Combination Therapy and BL-B01D1+PD-1 Monoclonal Antibody in patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors, and to further explore the optimal dose and combination way.

Enrollment: 376 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Sign the informed consent form voluntarily and follow the protocol requirements;
2. Gender is not limited;
3. Age: ≥18 years old and ≤75 years old;
4. Expected survival time ≥3 months;
5. Patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors;
6. Agreed to provide primary tumors or metastases 2 years archive of tumor tissue samples or fresh tissue samples;
7. At least one measurable lesion meeting the RECIST v1.1 definition was required;
8. ECOG 0 or 1;
9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. No blood transfusion, no use of cell growth factors and/or platelet-raising drugs within 14 days before screening, and organ function levels must meet the criteria;
12. Blood coagulation function: international standardization ratio of 1.5 or less, and the part activated clotting time live enzymes ULN 1.5 or less;
13. Urinary protein ≤2+ or ≤1000mg/24h;
14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum or urine must be negative for pregnancy, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion criteria

1. Antitumor therapy such as chemotherapy or biological therapy was used within 4 weeks or 5 half-lives before the first dose in this study; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
2. Cohort using BL-B01D1, previously treated with an ADC drug with topoisomerase I inhibitor as toxin; Immunomodulatory drugs were administered within 2 weeks before the first dose in this study;
3. Systemic corticosteroids were required within 2 weeks before the first dose of the study;
4. Had received immunotherapy and developed grade ≥3 irAE or grade ≥2 immune-related myocarditis according to the CSCO guidelines;
5. History of severe heart disease;
6. QT prolongation, complete left bundle branch block, III degree atrioventricular block;
7. Active autoimmune and inflammatory diseases;
8. Other malignant tumors were diagnosed within 5 years before the first dose in this study;
9. Presence of: a) poorly controlled diabetes mellitus before starting study treatment; b) poorly controlled hypertension; c) history of hypertensive crisis or hypertensive encephalopathy;
10. Pulmonary disease defined as grade ≥3 according to CTCAE v5.0; The patient was diagnosed with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition. Patients with existing or a history of interstitial lung disease;
11. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
12. Patients with unstable pericardial effusion, pleural effusion, ascites and other serous cavity effusion;
13. Patients with active central nervous system metastasis;
14. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any ingredient of BL-B01D1 or SI-B003;
15. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
16. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection;
17. Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc;
18. Enrolled in another clinical trial within 4 weeks before the first dose of this study;
19. Patients who received live vaccine within 4 weeks before the first dose;
20. Patients with a history of mental illness or drug abuse who are unable to cooperate with clinical trial requirements;
21. The investigator did not consider it appropriate to apply other criteria for participation in the trial.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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376 participants in 1 patient group

SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody

Experimental group

Description:

Participants received SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.

Treatment:

Drug: SI-B003

Drug: PD-1 Monoclonal Antibody

Drug: BL-B01D1