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 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.

Study Overview

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

Detailed Description

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.

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

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute and Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital
  • Gansu
    • Lanzhou, Gansu, China, 73000
      • The First Hospital of Lanzhou University
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital - Oncology
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's Hospital
    • Linyi, Shandong, China, 276001
      • LinYi Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital ,Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center (NCC)

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 ≤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. Has 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab + Fruquintinib; Participants with one of the tumors will be enrolled: GC,CRC and NSCLC	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 - 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

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, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; 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

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