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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03666143
• Other study ID #: BGB-900-103
• Secondary ID: CTR20181404
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2018
• Est. completion date: January 5, 2023

Study information

• Verified date: December 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: January 5, 2023
• Est. primary completion date: January 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• Sitravatinib
Administered orally as a capsule
• Tislelizumab
Administered intravenously

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Australia,  China, 

References & Publications (2)

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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)	Number of participants with treatment-emergent AEs (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs; TEAE was defined as an adverse event that had an onset date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study drug(s) or initiation of a new anticancer therapy, whichever occurs first.	Up to approximately 4 years and 2 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) as determined by the investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.	Up to approximately 4 years and 2 months
Secondary	Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response until the first documentation of progressive disease, whichever comes first, as assessed by the investigator using RECIST v1.1. Results are reported for cohorts with responders, defined as CR or PR. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.	Up to approximately 4 years and 2 months
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of participants with best overall response as CR, PR, or stable disease (SD) as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.	Up to approximately 4 years and 2 months
Secondary	Progression-free Survival (PFS)	PFS is defined as the time from the date of first dose to the date of first documentation of progressive disease or death, whichever comes first, as assessed by the investigator using RECIST v1.1. Efficacy was evaluated by cohort, as pre-specified in the statistical analysis plan.	Up to approximately 4 years and 2 months
Secondary	Maximum Plasma Concentration (Cmax) for Sitravatinib		Predose and up to 24 hours post dose on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 21 (C1D21); 21 days per cycle
Secondary	Time to Maximum Plasma Concentration (Tmax) for Sitravatinib		Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Time Point (AUC(0-t)) for Sitravatinib		Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
Secondary	Clearance After Oral Administration (CL/F) for Sitravatinib		Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
Secondary	Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUC(0-tau)) for Sitravatinib		Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
Secondary	Observed Accumulation Ratio (Ro) for AUC0-tau for Sitravatinib	Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation	Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle
Secondary	Observed Accumulation Ratio (Ro) for Cmax for Sitravatinib	Presented as geometric mean ratio and confidence interval, transformed from the difference of least square means and confidence interval of the least square differences in the logarithmic scale by exponentiation	Predose and up to 24 hours post dose on C1D1 and C1D21; 21 days per cycle