A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Patients With Advanced Solid Tumors.

Study Overview
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Brief Summary
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This is an open-label, multicenter, non-randomized Phase 1b clinical trial for patients with histologically or cytologically confirmed locally advanced or metastatic tumors including non-squamous or squamous NSCLC, RCC, OC, or melanoma.

Detailed Description
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All patients will receive sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg IV once every 3 weeks until occurrence of PD, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. There will be 9 cohorts in the study. Approximately 20 patients will be enrolled into each cohort. The patients will be enrolled according to their tumor type and prior anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody treatment. 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 (China-only): 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, aive, advanced or metastatic, non-squamous NSCLC Cohort I: PD-L1 positive,naive, advanced or metastatic, squamous NSCLC

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Sitravatinib
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Patients 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 Exclusion Criteria: 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. 8. 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 9. Known history of HIV infection 10. Patients with active hepatitis C infection. 11. Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drugs 12. Prior allogeneic stem cell transplantation or organ transplantation 13. Hypersensitivity to tislelizumab or sitravatinib, to any ingredient in the formulation, or to any component of the container 14. Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring within 6 months before first dose of study drugs 15. Concurrent participation in another therapeutic clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-PD-1/PD-L1 antibody refractory/resistant NSCLC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: Anti-PD-1/PD-L1 antibody naïve NSCLC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: Anti-PD-1/PD-L1 antibody refractory/resistant RCC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: Metastatic or advanced RCC without prior systemic therapy<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: Anti-PD-1/PD-L1 naïve recurrent / platinum resistant OC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: Anti-PD-1/PD-L1 treated metastatic, squamous NSCLC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: Anti-PD-1/PD-L1 antibody R/R melanoma<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: PD-L1 positive, naïve, advanced or metastatic, non-sq NSCLC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|
| Experimental: PD-L1 positive, naïve, advanced or metastatic, sq NSCLC<br> | Drug: Sitravatinib<br>* 120 mg orally once daily in combination with tislelizumab<br>* Other names: MGCD516;Drug: Tislelizumab<br>* 200 mg IV once every 3 weeks<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0 |  | All AEs and SAEs will be reported until either 30 days after last dose of study drug(s) or initiation of new anticancer therapy, whichever occurs first. Immune-related should be reported until 90 days after the last dose of tislelizumab |