A Study of Fruquintinib in Combination with Tislelizumab in Advanced Solid Tumors
- Conditions
- Triple Negative Breast CancerEndometrial CancerSolid Tumor, Unspecified, AdultColorectal Cancer
- Interventions
- Registration Number
- NCT04577963
- Lead Sponsor
- Hutchison Medipharma Limited
- Brief Summary
This is an open-label, multi-center, non-randomized, Phase 1b/2 study to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with locally advanced or metastatic solid tumors. This study will be conducted in 2 parts; a Safety Lead-in Phase (Part 1) and a Dose Expansion Phase (Part 2).
The Safety Lead-in Phase, open to any-comer solid tumors, will determine the RP2D. The RP2D will be administered to 3 cohorts of patients in the Dose Expansion Phase.
* Cohort A: Advanced or Metastatic Triple Negative Breast Cancer (TNBC) (IO-treated)
* Cohort B: Advanced or Metastatic Triple Negative Breast Cancer (TNBC) (IO-Naïve)
* Cohort C: Advanced or Metastatic Endometrial Cancer (EC) (IO-Naïve)
* Cohort D: Advanced or Metastatic Colorectal Cancer (mCRC) (IO-Naïve)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 52
- Willing and able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines;
- Age ≥18 years;
- Histologically or cytologically documented, advanced or metastatic Triple Negative Breast Cancer, histologically or cytologically documented, advanced or metastatic endometrial carcinoma, histologically or cytologically confirmed advanced or metastatic, unresectable adenocarcinoma of the colon or rectum.
- Tumor tissue (archival or fresh tumor tissues as formalin-fixed paraffin-embedded blocks or approximately 15 unstained slides) for central laboratory assessment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
- At least 1 measurable lesion as defined by RECIST v1.1.
- Has at screening any central nervous system metastasis and/or leptomeningeal disease.
- Except for Cohort A, 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 a VEGFR-TKI or anti-VEGFR antibody (eg, ramucirumab).
- Except for Cohort D, prior treatment with an anti-VEGFR antibody (eg, bevacizumab).
- Tumor tissue (archival or fresh tumor tissues as formalin-fixed paraffin-embedded blocks or approximately 15 unstained slides) for central laboratory assessment.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 Fruquintinib Patients will be enrolled to one of the following expansion cohorts: * Cohort A: TNBC (immuno-oncology \[IO\]-treated in the metastatic setting) * Cohort B: TNBC (IO-Naïve in the metastatic setting) * Cohort C: EC * Cohort D: MSS CRC Part 1 Fruquintinib Approximately 6-12 patients with locally advanced or metastatic solid tumors will be enrolled to receive fruquintinib in combination with tislelizumab and assessed for DLTs during the 28-day DLT observation period Part 1 Tislelizumab Approximately 6-12 patients with locally advanced or metastatic solid tumors will be enrolled to receive fruquintinib in combination with tislelizumab and assessed for DLTs during the 28-day DLT observation period Part 2 Tislelizumab Patients will be enrolled to one of the following expansion cohorts: * Cohort A: TNBC (immuno-oncology \[IO\]-treated in the metastatic setting) * Cohort B: TNBC (IO-Naïve in the metastatic setting) * Cohort C: EC * Cohort D: MSS CRC
- Primary Outcome Measures
Name Time Method Adverse Events by type, frequency, and severity At the end of Cycle 1 (each cycle is 28 days) To assess the safety and tolerability by monitoring AEs characterized by type, frequency, severity per NCI-CTCAE v5.0
Recommended Phase 2 Dose At the end of Cycle 1 (each cycle is 28 days) To confirm the RP2D of fruquintinib in combination with tislelizumab
Objective Response Rate Up to 18 months To evaluate the objective response rate (ORR) as assessed by the investigator in subjects with advanced or metastatic TNBC or EC or CRC when treated with fruquintinib in combination with tislelizumab
- Secondary Outcome Measures
Name Time Method Maximum plasma concentrations of fruquintinib with blood sampling Up to 18 months Blood samples will be taken to measure levels of fruquintinib
Disease Control Rate (DCR) Up to 24 months The incidence of complete response, partial response, and stable disease
Maximum serum concentrations of tislelizumab with blood sampling Up to 18 months Blood samples will be taken to measure levels of tislelizumab
Progression-free Survival Up to 24 months To further evaluate efficacy of fruquintinib in combination with tislelizumab in patients with advanced or metastatic TNBC or EC per investigator assessment
Clinical Benefit Rate Up to 24 months The incidence of partial response and stable disease
Duration of Response Up to 24 months he duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recroded
Overall Survival Up to 36 months The period from date of enrollment to date of death
Changes from baseline in biomarkers Up to 18 months To detect the expression biomarkers in tumor tissues of patients
Incidence of ADA to tislelizumab Up to 18 months To evaluate the immunogenicity of fruquintinib in combination with tislelizumab
Trial Locations
- Locations (16)
Florida Cancer Specialists - FCS South
🇺🇸Port Charlotte, Florida, United States
Florida Cancer Specialists - East (FCS East)
🇺🇸West Palm Beach, Florida, United States
Tennessee Oncology-Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Messino Cancer Center
🇺🇸Asheville, North Carolina, United States
Women and Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
Oklahoma University Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Tennesse Oncology
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Florida Cancer Specialists Panhandle
🇺🇸Tallahassee, Florida, United States
Highlands Oncology
🇺🇸Springdale, Arkansas, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Florida Cancer Center North
🇺🇸Saint Petersburg, Florida, United States
HOC AON Baton Rouge / Sarah Cannon
🇺🇸Baton Rouge, Louisiana, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Colorado
🇺🇸Aurora, Colorado, United States