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

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Tislelizumab; Drug: Sitravatinib

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia
      • Blacktown Cancer and Haematology Centre
  • Queensland
    • South Brisbane, Queensland, Australia
      • Icon Cancer Foundation
  • Victoria
    • Heidelberg, Victoria, Australia
      • Austin Hospital
    • Melbourne, Victoria, Australia
      • Nucleus Network
    • Melbourne, Victoria, Australia
      • Monash Health
  • Western Australia
    • Perth, Western Australia, Australia
      • Linear Clinical Research Limited
• China
  • Beijing, China
    • Beijing Cancer Hospital
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital
    • Beijing, Beijing, China
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Cancer Hospital Chinese Academy of Medical Science
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Guangdong General Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China
      • Renji Hospital Shanghai Jiaotong University School of Medicine
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. 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
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.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): January 5, 2023
• Study Completion (Actual): January 5, 2023

Study Registration Dates

• First Submitted: August 21, 2018
• First Submitted That Met QC Criteria: September 9, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BGB-900-103; CTR20181404 (Registry Identifier: Center for drug evaluation, CFDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes