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

NCT04716634 | Completed Phase 2 Results DMC

• 2 other identifiers: BGB-A317-fruquintinib-201CTR20211070
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 13

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.

Conditions

Advanced Solid Tumors

Keywords

Solid tumors

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Progression-Free Survival (PFS) as Assessed by Investigator Based on RECIST v1.1

  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

  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

  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

  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)

  From the first dose of the study treatment to date of death from any cause (up to 2 years and 9 months)

Study Arms (3)

Gastric Cancer (GC): Tislelizumab and Fruquintinib

EXPERIMENTAL

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; Drug: Fruquintinib

Colorectal Cancer (CRC): Tislelizumab and Fruquintinib

EXPERIMENTAL

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; Drug: Fruquintinib

PD-L1 + NSCLC: Tislelizumab and Fruquintinib

EXPERIMENTAL

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; Drug: Fruquintinib

Interventions

Tislelizumab DRUG

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

Also known as: BGB-A317

Colorectal Cancer (CRC): Tislelizumab and Fruquintinib; Gastric Cancer (GC): Tislelizumab and Fruquintinib; PD-L1 + NSCLC: Tislelizumab and Fruquintinib

Fruquintinib DRUG

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

Also known as: HMPL-013

Colorectal Cancer (CRC): Tislelizumab and Fruquintinib; Gastric Cancer (GC): Tislelizumab and Fruquintinib; PD-L1 + NSCLC: Tislelizumab and Fruquintinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 less than or equal to (\<=) 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

You may not qualify if:

• Had 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.

Sponsors & Collaborators

• BeiGene: lead
• Hutchison Medipharma Limited: collaborator

Study Sites (13)

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

The First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

Location

Liaocheng Peoples Hospital

Liaocheng, Shandong, 252000, China

Location

Linyi Cancer Hospital

Linyi, Shandong, 276001, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Asan Medical Center

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

MeSH Terms

Interventions

tislelizumab; HMPL-013

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Jian Li

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 20, 2021
• Study Start: April 19, 2021
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: March 25, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

CN (10); KR (3)