Clinical trial NCT04577963: A Study of Fruquintinib in Combination with Tislelizumab in Advanced Solid Tumors
Official title: An Open-Label, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Fruquintinib in Combination with Tislelizumab in Patients with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Triple Negative Breast Cancer
Endometrial Cancer
Solid Tumor, Unspecified, Adult
Colorectal Cancer
Keywords: Breast cancer
Triple negative
Her2-
HR-
ER-
PR-
Her2 negative
HR negative
ER negative
PR negative
TNBC
VEGF
VEGFR
Endometrial cancer
Colon
Rectal
mCRC
Colorectal
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: BeiGene
First posted: 2020-10-08
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines;
2. Age ≥18 years;
3. 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.
4. Tumor tissue (archival or fresh tumor tissues as formalin-fixed paraffin-embedded blocks or approximately 15 unstained slides) for central laboratory assessment.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
6. At least 1 measurable lesion as defined by RECIST v1.1.

Exclusion Criteria:

1. Has at screening any central nervous system metastasis and/or leptomeningeal disease.
2. 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.
3. Prior treatment with a VEGFR-TKI or anti-VEGFR antibody (eg, ramucirumab).
4. Except for Cohort D, prior treatment with an anti-VEGFR antibody (eg, bevacizumab).
5. Tumor tissue (archival or fresh tumor tissues as formalin-fixed paraffin-embedded blocks or approximately 15 unstained slides) for central laboratory assessment.
6. 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: Adverse Events by type, frequency, and severity
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Recommended Phase 2 Dose
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Objective Response Rate
timeFrame: Up to 18 months
Secondary outcomes:
measure: Maximum plasma concentrations of fruquintinib with blood sampling
timeFrame: Up to 18 months
measure: Maximum serum concentrations of tislelizumab with blood sampling
timeFrame: Up to 18 months
measure: Progression-free Survival
timeFrame: Up to 24 months
measure: Changes from baseline in biomarkers
timeFrame: Up to 18 months
measure: Incidence of ADA to tislelizumab
timeFrame: Up to 18 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
measure: Clinical Benefit Rate
timeFrame: Up to 24 months
measure: Duration of Response
timeFrame: Up to 24 months
measure: Overall Survival
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Port Charlotte
country: United States
facility: Florida Cancer Specialists - FCS South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Center North
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists Panhandle
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East (FCS East)
state: Florida
city: Baton Rouge
country: United States
facility: HOC AON Baton Rouge / Sarah Cannon
state: Louisiana
city: Asheville
country: United States
facility: Messino Cancer Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma University Stephenson Cancer Center
state: Oklahoma
city: Providence
country: United States
facility: Women and Infants Hospital of Rhode Island
state: Rhode Island
city: Chattanooga
country: United States
facility: Tennessee Oncology-Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennesse Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Hutchison MediPharma International
name: William Schelman, MD, PhD
role: STUDY_DIRECTOR
References: