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

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

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.

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

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