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

NCT ID: NCT04716634

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-19
• Study Completion Date: 2024-02-22

Brief Summary

This was 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 was conducted in 2 parts. Part 1 was the safety run-in stage to determine dose-limiting toxicity (DLT) and recommended Phase 2 dose (RP2D). Part 2 assessed 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

This was 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 was conducted in 2 parts.

Part 1 of the study was the safety run-in stage which assessed dose-limiting toxicities (DLTs) and RP2D. Part 2 began at RP2D. Participants enrolled in Part 1 at RP2D were counted towards Part 2; up to approximately 30 patients per cohort were enrolled at RP2D.

The primary outcome measure of the study was ORR as assessed by the investigator as per response evaluation criteria in solid tumors (RECIST) version (v) 1.1. Tislelizumab and fruquintinib were administered until disease progression, intolerable toxicity, death, withdrawal of consent or until the study terminates.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gastric Cancer (GC): Tislelizumab and Fruquintinib

Participants with advanced or metastatic, unresectable GC received fruquintinib 5 milligrams (mg) daily (3 weeks receiving fruquintinib followed by 1 week off) in combination with tislelizumab 300 mg intravenously on Day 1 of every 4-week cycle (each cycle of 28-days) until disease progression, unacceptable toxicity, or withdrawal for other reasons, whichever occurred first.

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.

Fruquintinib

Intervention Type: DRUG

Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI)

Colorectal Cancer (CRC): Tislelizumab and Fruquintinib

Participants with advanced or metastatic, unresectable CRC received fruquintinib 5 mg daily (3 weeks receiving fruquintinib followed by 1 week off) in combination with tislelizumab 300 mg intravenously on Day 1 of every 4-week cycle (each cycle of 28-days) until disease progression, unacceptable toxicity, or withdrawal for other reasons, whichever occurred first.

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.

Fruquintinib

Intervention Type: DRUG

Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI)

PD-L1 + NSCLC: Tislelizumab and Fruquintinib

Participants with programmed cell death protein ligand-1 (PD-L1) expression, and advanced or metastatic, unresectable non-small cell lung cancer (NSCLC) received fruquintinib 5 mg daily (3 weeks receiving fruquintinib followed by 1 week off) in combination with tislelizumab 300 mg intravenously on Day 1 of every 4-week cycle (each cycle of 28-days) until disease progression, unacceptable toxicity, or withdrawal for other reasons, whichever occurred first.

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.

Fruquintinib

Intervention Type: DRUG

Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI)

Interventions

Tislelizumab

Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.

Intervention Type: DRUG

Fruquintinib

Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI)

Intervention Type: DRUG

Other Intervention Names

BGB-A317; HMPL-013

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent form (ICF) and able to comply with study requirements.

2. At least 1 measurable lesion as defined by RECIST v1.1

3. Tumor tissue (archival tumor tissues as formalin-fixed paraffin-embedded blocks or approximately 15 unstained slides) for central laboratory assessment

4. Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=) 1

5. 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

Exclusion Criteria

1. Had at screening any central nervous system metastasis and/or leptomeningeal disease

2. 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

3. Prior treatment with VEGFR-TKI or anti-VEGFR antibody (eg, ramucirumab)

4. 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

5. 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.

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

Sponsors

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: collaborator

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jian Li

Role: STUDY_DIRECTOR

BeiGene

Locations

Fujian Cancer Hospital

Fuzhou, Fujian, China

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Shandong Cancer Hospital

Jinan, Shandong, China

Liaocheng Peoples Hospital

Liaocheng, Shandong, China

Linyi Cancer Hospital

Linyi, Shandong, China

West China Hospital, Sichuan University

Chengdu, Sichuan, 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

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Asan Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

Countries

China; South Korea

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CTR20211070

Identifier Type: OTHER

Identifier Source: secondary_id

BGB-A317-fruquintinib-201

Identifier Type: -

Identifier Source: org_study_id