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

BeiGene

Status and phase: Completed; Phase 2

Conditions: Advanced Solid Tumors

Treatments: Drug: Tislelizumab; Drug: Fruquintinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04716634

CTR20211070 (Other Identifier)

BGB-A317-fruquintinib-201

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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84 participants in 3 patient groups

Gastric Cancer (GC): Tislelizumab and Fruquintinib

Experimental group

Description:

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.

Treatment:

Drug: Fruquintinib

Drug: Tislelizumab

Colorectal Cancer (CRC): Tislelizumab and Fruquintinib

Experimental group

Description:

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.

Treatment:

Drug: Fruquintinib

Drug: Tislelizumab

PD-L1 + NSCLC: Tislelizumab and Fruquintinib

Experimental group

Description:

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.

Treatment:

Drug: Fruquintinib

Drug: Tislelizumab