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

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

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng Peoples Hospital
    • Linyi, Shandong, China, 276001
      • Linyi Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
• Korea, Republic of
  • Gyeonggi-do
    • Goyangsi, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
    • Seongnamsi, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05505
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Key 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

Key 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Tislelizumab; Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.; Other Names: BGB-A317; Drug: Fruquintinib; Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI); Other Names: HMPL-013
Experimental: 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.	Drug: Tislelizumab; Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.; Other Names: BGB-A317; Drug: Fruquintinib; Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI); Other Names: HMPL-013
Experimental: 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.	Drug: Tislelizumab; Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD 1.; Other Names: BGB-A317; Drug: Fruquintinib; Fruquintinib is a potent, oral VEGFR tyrosine kinase inhibitor (TKI); Other Names: HMPL-013

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)	A DLT was defined as 1 of the following toxicities (Grade 3 or 4 Hematologic or Nonhematologic toxicities) occurring during the DLT assessment window and considered by the investigator to be related to 1 or more study drugs. All toxicities or adverse events (AEs) were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).	Up to 28 Days
Part 1: Recommended Phase 2 Dose (RP2D)	RP2D for Part 2 was determined by evaluating safety and DLTs in Part 1 participants.	Up to 28 Days
Objective Response Rate (ORR) as Assessed by the Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1	ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From date of randomization until the date of first documented progression or death from any cause, whichever came first (up to 2 years and 9 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as Assessed by Investigator Based on RECIST v1.1	PFS was defined as the time from the date of the first dose of study drug(s) to the date of the confirmed documentation of progressive disease (PD) or death, whichever occurs first. Median PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	From date of first dose of study drug until the date of first documented progression or death from any cause, whichever came first (up to 2 years and 9 months)
Disease Control Rate (DCR) as Assessed by the Investigator Based on RECIST v1.1	DCR was defined as the percentage of participants whose best overall response is CR, PR, or stable disease (SD) as assessed by investigator as per RECIST v1.1. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	From date of randomization until the date of first documented progression or death from any cause, whichever came first (up to 2 years and 9 months)
Clinical Benefit Rate (CBR) as Assessed by the Investigator Based on RECIST v1.1	CBR was defined as the percentage of participants whose best overall response is CR, PR, or durable stable disease (SD) as assessed by the investigator per RECIST v1.1. Per RECIST v1.1., CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	From date of randomization until the date of first documented progression or death from any cause, whichever came first (up to 2 years and 9 months)
Duration of Response (DOR) as Assessed by The Investigator Based on RECIST v1.1	DOR was defined as the time from the first occurrence of documented objective response to the time of progression as assessed by investigator per RECIST v1.1 or death from any cause, whichever occurs first. Median DOR was estimated using the Kaplan-Meier method.	From the first objective response to the date of first documentation of disease progression or death, whichever occurs first (up to 2 years and 9 months)
Overall Survival (OS)	OS was defined as the time from the date of first dose to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.	From the first dose of the study treatment to date of death from any cause (up to 2 years and 9 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, Grade 3 or Higher TEAEs, TEAEs Leading to Death, TEAEs Related to Tislelizumab, TEAEs Related to Fruquintinib	A TEAE was defined as an AE that had an onset date or a worsening in severity from baseline (pre-treatment) on or after the first dose of study drug(s) and up to 30 days following study drug(s) discontinuation or initiation of new anticancer therapy, whichever occurred first determined according to NCI-CTCAE v5.0. Treatment emergent serious Adverse Events (TESAEs): any untoward medical occurrence at any dose: resulted in death; was life threatening; required prolong inpatient hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect or was considered a significant medical event by the investigator. AEs were graded for severity using NCI-CTCAE v5.0, where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE. The TEAEs leading to death in this data table exclude death due to disease under study.	From the date of the first dose of study drug up to 30 days after the last dose of study drug; up to approximately 2 years and 5 months.

Collaborators and Investigators

• Sponsor: BeiGene
• Collaborators: Hutchison Medipharma Limited
• Investigators: Study Director: Jian Li, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: BGB-A317-fruquintinib-201; CTR20211070 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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