Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Various Combinations of BGB-A425 and LBL-007 with Tislelizumab in Patients with Advanced Solid Tumors
Overview
- Phase
- Phase 1/2
- Status
- Completed
- Sponsor
- Beigene Ltd., Beigene Ltd.
- Enrollment
- 48
- Locations
- 15
- Primary Endpoint
- Phase 1(Dose Escalation) & Phase 2(Safety Lead-in): Adverse events (AEs) and serious AE (SAEs) as characterized by type, frequency, severity (as graded by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0), timing, seriousness, and relationship to study therapy; laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing; AEs meeting protocol defined dose limiting toxicity (DLT) criteria
Overview
Brief Summary
Phase 1 (Dose Escalation):
• To assess the safety and tolerability of BGB-A425 in combination with tislelizumab in patients with advanced solid tumors • To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) of BGB-A425 in combination with tislelizumab
Phase 2 (Safety Lead-in):
• To assess the safety and tolerability of BGB-A425 in combination with LBL-007 and tislelizumab or LBL-007 in combination with tislelizumab in patients with advanced solid tumors • To determine the MTD or MAD and RP2D/ recommended dose for expansion of LBL-007 in combination with BGB-A425 and tislelizumab, and LBL-007 in combination with tislelizumab
Phase 2 (Dose Expansion):
• To evaluate antitumor activity based on objective response rate (ORR) of various combinations of BGB-A425 and LBL-007 with tislelizumab in selected tumor types
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Adequate organ function
- •Phase 1 Dose Escalation + Phase 2 Safety Lead-In: Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for which treatment is not available or not tolerated
- •Phase 2 Dose-Expansion: Participants with one of the following histologically or cytologically confirmed solid tumors: For HNSCC participants in cohort 1,4 and 6 (PD-L1 positive): Recurrent/metastatic head and neck squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and/or larynx whose tumor is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy; For NSCLC participants in Cohort 2, 5 and 7 (PD-L1 positive): Locally recurrent Stage IIIB, stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer; For RCC participants in Cohort 3: Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology.
Exclusion Criteria
- •NSCLC patients with known EGFR mutation, BRAF mutation, ALK fusion, or ROS1 fusion
- •Chemotherapy, radiotherapy, immunotherapy or any investigational therapies within 28 days (PH 2 Safety Lead-In) or 14 days (PH 2 Dose Expansion) or 5 half-lives of (whichever is shorter) of first administration of study drug(s)
- •With infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 14 days prior to the first dose of study drug(s), or a requirement for chronic prophylactic treatment with antibiotics.
- •Concurrent participation in another therapeutic clinical trial
- •Received prior therapies targeting TIM-3and/or LAG3
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Active autoimmune diseases or history of autoimmune diseases that may relapse.
- •Interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases
- •Uncontrolled diabetes or significant cardiac issues
- •Infections requiring systemic antibacterial, antifungal, or antiviral therapy
Outcomes
Primary Outcomes
Phase 1(Dose Escalation) & Phase 2(Safety Lead-in): Adverse events (AEs) and serious AE (SAEs) as characterized by type, frequency, severity (as graded by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0), timing, seriousness, and relationship to study therapy; laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing; AEs meeting protocol defined dose limiting toxicity (DLT) criteria
Phase 1(Dose Escalation) & Phase 2(Safety Lead-in): Adverse events (AEs) and serious AE (SAEs) as characterized by type, frequency, severity (as graded by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0), timing, seriousness, and relationship to study therapy; laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing; AEs meeting protocol defined dose limiting toxicity (DLT) criteria
Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): The MTD or MAD is defined as the highest dose at which < 33% of the patients experience a DLT
Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): The MTD or MAD is defined as the highest dose at which < 33% of the patients experience a DLT
Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): The RP2D/recommended dose for expansion of the combination treatments will be determined based upon the MTD or MAD, and will also take into consideration the longterm tolerability, PK, efficacy, and any other relevant data as available
Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): The RP2D/recommended dose for expansion of the combination treatments will be determined based upon the MTD or MAD, and will also take into consideration the longterm tolerability, PK, efficacy, and any other relevant data as available
Phase 2 (Dose Expansion): ORR as determined from investigator derived tumor assessments per RECIST v1.1
Phase 2 (Dose Expansion): ORR as determined from investigator derived tumor assessments per RECIST v1.1
Secondary Outcomes
- Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): Efficacy evaluations: ORR, duration of response (DOR), and disease control rate (DCR) will be determined from investigator derived tumor assessments per RECIST v1.1
- Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): PK: Maximum observed plasma concentration (Cmax), minimum observed plasma concentration (Cmin), time to maximum plasma concentration (Tmax), half-life (t1/2), area under the concentration-time curve from zero to 21 days (AUC0-21d), CL, and apparent volume of distribution (Vz) for BGB-A425 and LBL-007; Cmax and Cmin for tislelizumab
- Phase 1 (Dose Escalation) & Phase 2 (Safety Lead-in): Immunogenicity: Immunogenic responses to BGB-A425, LBL-007, and tislelizumab will be assessed by summarizing the number and percentage of patients who develop detectable antidrug antibodies
- Phase 2 (Dose Expansion): Progression-free survival (PFS), DOR, and DCR will be determined from investigator derived tumor assessments as per RECIST v1.1
- Phase 2 (Dose Expansion): Safety and tolerability: The safety of various combinations of BGB-A425 and LBL-007 with tislelizumab will be assessed throughout the study by monitoring AEs and SAEs per NCI-CTCAE v5.0, physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed
- Phase 2 (Dose Expansion): PK: PK parameters such as Cmax, Cmin, Tmax, t1/2, and AUC0-21d for BGB-A425 and LBL-007; Cmax and Cmin for tislelizumab
- Phase 2 (Dose Expansion): Immunogenicity: Immunogenic responses to BGB-A425, LBL-007, and tislelizumab will be assessed by summarizing the number and percentage of patients who develop detectable antidrug antibodies (ADAs).
Investigators
BeiGene Clinical Support
Scientific
Beigene Ltd.