A Phase II Clinical Study to Evaluate 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
Overview
- Phase
- Phase 2
- Intervention
- SI-B003
- Conditions
- Esophageal Cancer
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 268
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
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.
Detailed 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Sign the informed consent form voluntarily and follow the protocol requirements;
- •Gender is not limited;
- •Age: ≥18 years old and ≤75 years old;
- •Expected survival time ≥3 months;
- •Patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors;
- •Agreed to provide primary tumors or metastases 2 years archive of tumor tissue samples or fresh tissue samples;
- •At least one measurable lesion meeting the RECIST v1.1 definition was required;
- •ECOG 0 or 1;
- •The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
Exclusion Criteria
- •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;
- •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;
- •Systemic corticosteroids were required within 2 weeks before the first dose of the study;
- •Had received immunotherapy and developed grade ≥3 irAE or grade ≥2 immune-related myocarditis according to the CSCO guidelines;
- •History of severe heart disease;
- •QT prolongation, complete left bundle branch block, III degree atrioventricular block;
- •Active autoimmune and inflammatory diseases;
- •Other malignant tumors were diagnosed within 5 years before the first dose in this study;
- •Presence of: a) poorly controlled diabetes mellitus before starting study treatment; b) poorly controlled hypertension; c) history of hypertensive crisis or hypertensive encephalopathy;
- •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;
Arms & Interventions
SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody
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.
Intervention: SI-B003
SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody
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.
Intervention: BL-B01D1
SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody
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.
Intervention: PD-1 Monoclonal Antibody
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Up to approximately 24 months
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Recommended Phase II Dose (RP2D)
Time Frame: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study .
Secondary Outcomes
- Duration of response (DOR)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Disease control rate (DCR)(Up to approximately 24 months)