A Phase II Clinical Trial to Evaluate the Efficacy and Safety of BL-B01D1 Monotherapy, SI-B003 Monotherapy and BL-B01D1+SI-B003 Combination Therapy (BL-B01D1+SI-B003) in Patients With Extensive Stage Small Cell Lung Cancer (SCLC)
Overview
- Phase
- Phase 2
- Intervention
- BL-B01D1
- Conditions
- Small Cell Lung Cancer
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This phase II study is designed to investigate the efficacy and safety of BL-B01D1 monotherapy, SI-B003 monotherapy, and BL-B01D1+SI-B003 combination therapy in patients with extensive-stage small cell lung cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All subjects voluntarily participated in the study and signed informed consent;
- •Male or female aged ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Patients with extensive-stage small-cell Lung cancer confirmed by histopathology and/or cytology (according to Veterans Administration Lung Study Group (VALG) staging);
- •Cohort\_A cohort of patients with extensive-stage small cell lung cancer who had failed or were intolerant to 3 or more lines of systemic antitumor therapy. The so-called intolerance refers to the patients who have received standard treatment and have grade 3-4 adverse reactions, and the patients refuse to continue the original regimen.
- •Cohort\_B Stage I subjects with previous failure or intolerance to standard therapy for extensive-stage small cell lung cancer;
- •Cohort\_B Stage II patients who have not received any previous systemic anti-tumor therapy for extensive-stage small cell lung cancer;
- •Consent to provide archival tumor tissue specimens (10 unstained sections (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If participants cannot provide tumor tissue samples, they can be enrolled if they meet other inclusion and exclusion criteria, after the evaluation of the investigator;
- •Must have at least one measurable lesion according to RECIST v1.1 definition; Lesions that had been previously treated with radiation could be included in a measurable lesion only if there was definite disease progression after radiation therapy.
- •Organ function level must meet the following criteria:
Exclusion Criteria
- •Previous treatment with EGFR and HER3 monoclonal antibodies;
- •Antineoplastic therapy, including chemotherapy, biologic therapy, immunotherapy, definitive radiotherapy, major surgery (investigator-defined), or targeted therapy (including small-molecule tyrosine kinase inhibitors), has been administered within 4 weeks or 5 half-life cycles (whichever is shorter) before the first dose; Oral fluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks before the first dose;
- •Cohort\_B Stage II patients who had received any previous systemic therapy for extensive-stage SCLC were not eligible for the study;
- •Cohort\_B with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis, excluded;
- •Cohort\_B with history of use of immunomodulatory drugs (including but not limited to thymosin, interleukin-2, interferon, etc.) within 14 days before the first dose of study drug was excluded.
- •A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
- •severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias or Ⅲ degree atrioventricular block requiring clinical intervention;
- •prolonged QT interval at rest (QTc \> 450 msec in men or QTc \> 470 msec in women);
- •myocardial infarction, unstable angina, cardiac angioplasty or stent implantation, coronary artery/peripheral artery bypass grafting, New York Heart Association (NYHA) class III or IV congestive heart failure, cerebrovascular accident, or transient ischemic attack within 6 months before the first dose;
- •Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis);
Arms & Interventions
Study treatment
Participants received BL-B01D1 monotherapy, SI-B003 monotherapy or BL-B01D1 plus SI-B003 dual therapy 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
Study treatment
Participants received BL-B01D1 monotherapy, SI-B003 monotherapy or BL-B01D1 plus SI-B003 dual therapy 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
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 of SI-B003.
Secondary Outcomes
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Disease control rate (DCR)(Up to approximately 24 months)
- Duration of response (DOR)(Up to approximately 24 months)