Efficacy and Safety of Tislelizumab in Combination With Fruquintinib in Participants With Selected Solid Tumors

Study Overview
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Brief Summary
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This is an open label, multicenter, Phase 2 study designed to assess the efficacy and safety of tislelizumab in combination with fruquintinib in participants with advanced or metastatic, unresectable gastric cancer (GC), or colorectal cancer (CRC) or Non-small Cell Lung Cancer (NSCLC). The study will be conducted in 2 parts. Part 1 will be the safety run-in stage to determine dose-limiting toxicity (DLT) and recommended Phase 2 dose (RP2D). Part 2 will assess the preliminary efficacy of tislelizumab in combination with fruquintinib in participants as measured by the overall response rate (ORR) and other efficacy and safety profiles.

Detailed Description
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This is an open label, multicenter, Phase 2 study designed to assess the efficacy and safety of tislelizumab in combination with fruquintinib in patients with advanced or metastatic, unresectable GC, and CRC or NSCLC. The study will be conducted in 2 parts. Part 1 of the study will be the safety run-in stage which assesses dose-limiting toxicities (DLTs) and RP2D. Part 2 will begin at RP2D. Patients enrolled in Part 1 at RP2D will be counted towards Part 2; up to approximately 30 patients per cohort will be enrolled at RP2D. The primary outcome measure of the study is ORR as assessed by the investigator per RECIST v1.1. Tislelizumab and fruquintinib will be administered until disease progression, intolerable toxicity, death, withdrawal of consent or until the study terminates.

Official Title
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A Multicenter, Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Tislelizumab in Combination With Fruquintinib in Patients With Selected Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Fruquintinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed informed consent form (ICF) and able to comply with study requirements. At least 1 measurable lesion as defined by RECIST v1.1. Tumor tissue (archival tumor tissues as formalin-fixed paraffin-embedded blocks or approximately 15 unstained slides) for central laboratory assessment Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 Histologically or cytologically confirmed, advanced or metastatic, unresectable adenocarcinoma of gastric or esophagogastric junction or colon or rectum, and histologically or cytologically confirmed, locally advanced (Stage IIIB) not amenable to curative surgery or radiotherapy, or metastatic (Stage IV) NSCLC Key Exclusion Criteria: Has at screening any central nervous system metastasis and/or leptomeningeal disease. Prior therapy targeting CTLA-4, PD-1, PD-L1 or programmed cell death protein ligand-2 (PD-L2) or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. Prior treatment with VEGFR-TKI or anti-VEGFR antibody (eg, ramucirumab). Received more than 1 line of systemic treatment for advanced or metastatic, unresectable adenocarcinoma of gastric or esophagogastric junction, or more than 2 lines of systemic treatment for advanced or metastatic, unresectable adenocarcinoma of the colon or rectum, or prior systemic therapy for advanced or metastatic NSCLC. Active autoimmune diseases or history of autoimmune diseases that may relapse, or history of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including but not limited to pulmonary fibrosis, acute lung diseases, etc. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab + Fruquintinib<br>Participants with one of the tumors will be enrolled: GC,CRC and NSCLC | Drug: Tislelizumab<br>* Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.<br>* Other names: BGB-A317;Drug: Fruquintinib<br>* Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI)<br>* Other names: HMPL-013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 - Adverse Event (AE) | Assessed per NCI-CTCAE v5.0 | Up to 28 Days in Part 1 | 
| Part 1 - RP2D Of Fruquintinib In Combination With Tislelizumab |  | Up to 28 Days in Part 1 | 
| Part 2 - Objective Response Rate (ORR) | Assessed per RECIST v1.1 | through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2 - Progression-Free Survival (PFS) | Assessed per RECIST v1.1 | through study completion, an average of 3 years | 
| Part 2 - Disease Control Rate (DCR) | Assessed per RECIST v1.1 | through study completion, an average of 3 years | 
| Part 2 - Clinical Benefit Rate (CBR) | Assessed per RECIST v1.1 | through study completion, an average of 3 years | 
| Part 2 - Duration Of Response (DOR) |  | through study completion, an average of 3 years | 
| Part 2 - Overall Survival (OS) |  | through study completion, an average of 3 years | 
| Part 2 - Adverse Event | Assessed per NCI-CTCAE v5.0 | through study completion, an average of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors