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

NCT ID: NCT03666143

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2023-01-05

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

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sitravatinib + Tislelizumab

Sitravatinib 120 mg was administered orally once daily in combination with tislelizumab 200 mg intravenously (IV) once every 3 weeks

Group Type: EXPERIMENTAL

Sitravatinib

Intervention Type: DRUG

Administered orally as a capsule

Tislelizumab

Intervention Type: DRUG

Administered intravenously

Interventions

Sitravatinib

Administered orally as a capsule

Intervention Type: DRUG

Tislelizumab

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

MGCD516; BGB-A317; Tevimbra

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia

Icon Cancer Foundation

South Brisbane, Queensland, Australia

Monash Health

Clayton, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Nucleus Network

Melbourne, Victoria, Australia

Linear Clinical Research

Nedlands, Western Australia, Australia

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

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 Jilin University

Changchun, Jilin, 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 Municipality, China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

Australia; China

References

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 36808075 (View on PubMed)

Wang X, Pan H, Cui J, Chen X, Yoon WH, Carlino MS, Li X, Li H, Zhang J, Sun J, Guo J, Cui C. SAFFRON-103: a phase Ib study of sitravatinib plus tislelizumab in anti-PD-(L)1 refractory/resistant advanced melanoma. Immunotherapy. 2024 Mar;16(4):243-256. doi: 10.2217/imt-2023-0130. Epub 2024 Jan 10.

Reference Type: DERIVED

PMID: 38197138 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CTR20181404

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-900-103

Identifier Type: -

Identifier Source: org_study_id