A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors
- Registration Number
- NCT03666143
- Lead Sponsor
- BeiGene
- Brief Summary
This was an open-label, multicenter, non-randomized Phase 1b clinical trial for participants with histologically or cytologically confirmed locally advanced or metastatic tumors including non-squamous or squamous non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), ovarian cancer (OC), or melanoma.
- Detailed Description
All participants received sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks until occurrence of progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. Participants were enrolled according to their tumor type and prior anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody treatment into the following cohorts:
* Cohort A: Anti-PD-1/PD-L1 antibody refractory/resistant metastatic, non-squamous NSCLC
* Cohort B: Anti-PD-1/PD-L1 antibody naïve metastatic, non-squamous NSCLC
* Cohort C: Anti-PD-1/PD-L1 antibody refractory/resistant metastatic or advanced RCC
* Cohort D: Metastatic or advanced RCC without prior systemic therapy
* Cohort E: Anti-PD-1/PD-L1 antibody naïve recurrent and platinum resistant epithelial OC
* Cohort F: Anti-PD-1/PD-L1 antibody treated metastatic, squamous NSCLC
* Cohort G: Anti-PD-1/PD-L1 antibody refractory/resistant unresectable or metastatic melanoma
* Cohort H: PD-L1 positive, locally advanced or metastatic, non-squamous NSCLC without prior systemic treatment in the metastatic setting
* Cohort I: PD-L1 positive, locally advanced or metastatic, squamous NSCLC without prior systemic treatment in the metastatic setting
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 216
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the Schedule of Assessments
- Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
- At least 1 measurable lesion as defined by RECIST v1.1
- Provide archival tumor tissue (formalin-fixed paraffin-embedded block [FFPE] with tumor tissue or unstained slides), if available.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Adequate hematologic and end-organ function
- Participants with inactive/asymptomatic carrier, chronic, or active hepatitis B virus (HBV) must have HBV deoxyribonucleic acid (DNA) < 500 IU/mL (or 2500 copies/mL) at Screening
- Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drugs and have a negative serum pregnancy test ≤ 7 days of first dose of study drugs
- Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drugs
- Unacceptable toxicity on prior anti-PD-1/PD-L1 treatment
- Active leptomeningeal disease or uncontrolled brain metastasis
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Any active malignancy ≤ 2 years
- Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drugs
- History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases, including pulmonary fibrosis, acute lung diseases, etc.
- Severe chronic or active infections (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy, within 14 days prior to first dose of study drugs
- Known history of human immunodeficiency virus (HIV) infection
- Participants with active hepatitis C infection
- Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs
- Prior allogeneic stem cell transplantation or organ transplantation
- Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container
- Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring within 6 months before first dose of study drugs
- Concurrent participation in another therapeutic clinical trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sitravatinib + Tislelizumab Sitravatinib Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks Sitravatinib + Tislelizumab Tislelizumab Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) Up to approximately 4 years and 2 months Number of participants with treatment-emergent AEs (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs; TEAE was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study drug(s) or initiation of a new anticancer therapy, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Up to approximately 4 years and 2 months DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease, whichever comes first, as assessed by the investigator using RECIST v1.1. Results are reported for cohorts with responders, defined as CR or PR. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle Clearance After Oral Administration (CL/F) for Sitravatinib Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation
Objective Response Rate (ORR) Up to approximately 4 years and 2 months ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) as determined by the investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.
Disease Control Rate (DCR) Up to approximately 4 years and 2 months DCR is defined as the percentage of participants with best overall response as CR, PR, or stable disease (SD) as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.
Progression-free Survival (PFS) Up to approximately 4 years and 2 months PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease or death, whichever comes first, as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.
Time to Maximum Plasma Concentration (Tmax) for Sitravatinib Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle Maximum Plasma Concentration (Cmax) for Sitravatinib Predose and up to 24 hours post dose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21); 21 days per cycle Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle Observed Accumulation Ratio (Ro) for AUC0-tau for Sitravatinib Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation
Trial Locations
- Locations (19)
Icon Cancer Foundation
🇦🇺South Brisbane, Queensland, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Nucleus Network
🇦🇺Melbourne, Victoria, Australia
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China