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 Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors
Overview
- Phase
- Phase 2
- Intervention
- BL-B01D1
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 186
- 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 recurrent or metastatic head and neck squamous cell carcinoma and other solid tumors.
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 recurrent or metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) confirmed by histopathology and/or cytology:
- •Cohort\_A, B, and Cohort\_C Stage I patients who had failed or were intolerant to 1 or more lines of systemic therapy for recurrent or metastatic HNSCC (non-nasopharyngeal carcinoma);
- •Cohort\_C Stage II patients who had not received any previous systemic antitumor therapy (other than induction chemotherapy, neoadjuvant, or adjuvant therapy) for recurrent or metastatic HNSCC (non-nasopharyngeal); Treatment failure was defined as disease progression during or after systemic antitumor therapy.
- •Intolerance refers to the refusal of patients to continue the original regimen due to grade 3-4 adverse reactions after receiving standard treatment.
- •Note: Recurrence or disease progression within 6 months after the last chemotherapy of multimodal therapy was considered as the first line of treatment.
- •Consent to provide archival tumor tissue specimens (10-12 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.
Exclusion Criteria
- •Prior treatment with an ADC drug with a topoisomerase I inhibitor as a toxin.
- •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.
- •Non-squamous cell tissue confirmed by histopathology and/or cytology must be excluded.
- •Cohort\_C Stage II patients who had received any previous systemic therapy for recurrent or metastatic HNSCC (other than induction chemotherapy, adjuvant or neoadjuvant therapy) were excluded.
- •Cohort\_C with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis, excluded.
- •Cohort\_C cohort\_c who had received immunomodulatory drugs (including but not limited to thymosin, interleukin-2, interferon, etc.) within 14 days before the first dose of study drug was excluded.
- •Systemic corticosteroids (\> 10mg/ day of prednisone, or the equivalent of another corticosteroid) are required within 2 weeks before the first dose of the study dose; Exceptions were inhaled or topical corticosteroids or physiological replacement doses of corticosteroids for adrenal insufficiency.
- •A history of immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditis must be 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;
Arms & Interventions
Study treatment
Participants receive BL-B01D1, SI-B003 or BL-B01D1 + SI-B003 therapy in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.
Intervention: BL-B01D1
Study treatment
Participants receive BL-B01D1, SI-B003 or BL-B01D1 + SI-B003 therapy in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. 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.
Secondary Outcomes
- 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)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)