A Study of Fruquintinib in Combination With Tislelizumab in Advanced Solid Tumors

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04577963
• Other study ID #: 2020-013-00US3
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 9, 2021
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Hutchmed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: November 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Solid Tumor, Unspecified, Adult
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Fruquintinib
Oral VEGFR inhibitor
• Tislelizumab
PD-1 inhibitor

Locations

Country	Name	City	State
United States	Messino Cancer Center	Asheville	North Carolina
United States	University of Colorado	Aurora	Colorado
United States	HOC AON Baton Rouge / Sarah Cannon	Baton Rouge	Louisiana
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Tennessee Oncology-Chattanooga	Chattanooga	Tennessee
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennesse Oncology	Nashville	Tennessee
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Oklahoma University Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Florida Cancer Specialists - FCS South	Port Charlotte	Florida
United States	Women and Infants Hospital of Rhode Island	Providence	Rhode Island
United States	Florida Cancer Center North	Saint Petersburg	Florida
United States	Highlands Oncology	Springdale	Arkansas
United States	Florida Cancer Specialists Panhandle	Tallahassee	Florida
United States	Florida Cancer Specialists - East (FCS East)	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited	BeiGene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events by type, frequency, and severity	To assess the safety and tolerability by monitoring AEs characterized by type, frequency, severity per NCI-CTCAE v5.0	At the end of Cycle 1 (each cycle is 28 days)
Primary	Recommended Phase 2 Dose	To confirm the RP2D of fruquintinib in combination with tislelizumab	At the end of Cycle 1 (each cycle is 28 days)
Primary	Objective Response Rate	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	Up to 18 months
Secondary	Maximum plasma concentrations of fruquintinib with blood sampling	Blood samples will be taken to measure levels of fruquintinib	Up to 18 months
Secondary	Maximum serum concentrations of tislelizumab with blood sampling	Blood samples will be taken to measure levels of tislelizumab	Up to 18 months
Secondary	Progression-free Survival	To further evaluate efficacy of fruquintinib in combination with tislelizumab in patients with advanced or metastatic TNBC or EC per investigator assessment	Up to 24 months
Secondary	Changes from baseline in biomarkers	To detect the expression biomarkers in tumor tissues of patients	Up to 18 months
Secondary	Incidence of ADA to tislelizumab	To evaluate the immunogenicity of fruquintinib in combination with tislelizumab	Up to 18 months
Secondary	Disease Control Rate (DCR)	The incidence of complete response, partial response, and stable disease	Up to 24 months
Secondary	Clinical Benefit Rate	The incidence of partial response and stable disease	Up to 24 months
Secondary	Duration of Response	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	Up to 24 months
Secondary	Overall Survival	The period from date of enrollment to date of death	Up to 36 months