Clinical trial NCT04716634: Efficacy and Safety of Tislelizumab in Combination With Fruquintinib in Participants With Selected Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Solid Tumors
Keywords: Solid tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
Collaborators: name: Hutchison Medipharma Limited
First posted: 2021-01-20
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 Days
measure: Part 1: Recommended Phase 2 Dose (RP2D)
timeFrame: Up to 28 Days
measure: Objective Response Rate (ORR) as Assessed by the Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1
timeFrame: 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:
measure: Progression-Free Survival (PFS) as Assessed by Investigator Based on RECIST v1.1
timeFrame: 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)
measure: Disease Control Rate (DCR) as Assessed by the Investigator Based on RECIST v1.1
timeFrame: 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)
measure: Clinical Benefit Rate (CBR) as Assessed by the Investigator Based on RECIST v1.1
timeFrame: 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)
measure: Duration of Response (DOR) as Assessed by The Investigator Based on RECIST v1.1
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From the first dose of the study treatment to date of death from any cause (up to 2 years and 9 months)
measure: 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
timeFrame: 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.
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng Peoples Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Goyangsi
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnamsi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
Study officials:
affiliation: BeiGene
name: Jian Li
role: STUDY_DIRECTOR
References: