Clinical trial NCT03666143: A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors
Official title: A Phase 1b Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-09-11
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the Schedule of Assessments
2. 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)
3. At least 1 measurable lesion as defined by RECIST v1.1
4. Provide archival tumor tissue (formalin-fixed paraffin-embedded block \[FFPE\] with tumor tissue or unstained slides), if available.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
6. Adequate hematologic and end-organ function
7. 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
8. 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
9. 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

Exclusion Criteria:

1. Unacceptable toxicity on prior anti-PD-1/PD-L1 treatment
2. Active leptomeningeal disease or uncontrolled brain metastasis
3. Active autoimmune diseases or history of autoimmune diseases that may relapse
4. Any active malignancy ≤ 2 years
5. 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
6. History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases, including pulmonary fibrosis, acute lung diseases, etc.
7. 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
8. Known history of human immunodeficiency virus (HIV) infection
9. Participants with active hepatitis C infection
10. Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs
11. Prior allogeneic stem cell transplantation or organ transplantation
12. Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container
13. 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
14. Concurrent participation in another therapeutic clinical trial

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 4 years and 2 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 4 years and 2 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 4 years and 2 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 4 years and 2 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 4 years and 2 months
measure: Maximum Plasma Concentration (Cmax) for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21); 21 days per cycle
measure: Time to Maximum Plasma Concentration (Tmax) for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
measure: Clearance After Oral Administration (CL/F) for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
measure: Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
measure: Observed Accumulation Ratio (Ro) for AUC0-tau for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
measure: Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib
timeFrame: Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Foundation
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Guo J, Zhou Q, Huang D, Yu X, Zhao J, Chu Q, Ma Z, Millward M, Gao B, Goh J, Markman B, Voskoboynik M, Gan H, Coward J, Chen C, Xiang X, Qui J, Xu Y, Yang L, Wu YL. A phase 1b study to assess safety, tolerability, pharmacokinetics, and preliminary antitumor activity of sitravatinib in combination with tislelizumab in patients (pts) with advanced solid tumors. Chinese Society of Clinical Oncology. 2019.
citation: Zhao J, Yu X, Huang D, Ma Z, Gao B, Cui J, Chu Q, Zhou Q, Sun M, Day D, Wu J, Pan H, Wang L, Voskoboynik M, Wang Z, Liu Y, Li H, Zhang J, Peng Y, Wu YL. SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer. J Immunother Cancer. 2023 Feb;11(2):e006055. doi: 10.1136/jitc-2022-006055.