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

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Triple Negative Breast Cancer; Endometrial Cancer; Solid Tumor, Unspecified, Adult
• Intervention / Treatment: Drug: Fruquintinib; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Port Charlotte, Florida, United States, 33980
      • Florida Cancer Specialists - FCS South
    • Saint Petersburg, Florida, United States, 33709
      • Florida Cancer Center North
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists Panhandle
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists - East (FCS East)
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • HOC AON Baton Rouge / Sarah Cannon
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Messino Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Stephenson Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital of Rhode Island
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology-Chattanooga
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Tennesse Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; 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	Drug: Fruquintinib; Oral VEGFR inhibitor; Other Names: HMPL-013; Drug: Tislelizumab; PD-1 inhibitor; Other Names: BGB-A317
Experimental: Part 2; 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	Drug: Fruquintinib; Oral VEGFR inhibitor; Other Names: HMPL-013; Drug: Tislelizumab; PD-1 inhibitor; Other Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentrations of fruquintinib with blood sampling	Blood samples will be taken to measure levels of fruquintinib	Up to 18 months
Maximum serum concentrations of tislelizumab with blood sampling	Blood samples will be taken to measure levels of tislelizumab	Up to 18 months
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
Changes from baseline in biomarkers	To detect the expression biomarkers in tumor tissues of patients	Up to 18 months
Incidence of ADA to tislelizumab	To evaluate the immunogenicity of fruquintinib in combination with tislelizumab	Up to 18 months
Disease Control Rate (DCR)	The incidence of complete response, partial response, and stable disease	Up to 24 months
Clinical Benefit Rate	The incidence of partial response and stable disease	Up to 24 months
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
Overall Survival	The period from date of enrollment to date of death	Up to 36 months

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Collaborators: BeiGene
• Investigators: Study Director: William Schelman, MD, PhD, Hutchison MediPharma International

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: October 4, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: VEGF; Breast cancer; TNBC; Endometrial cancer; Colon; VEGFR; Colorectal; Triple negative; mCRC; Her2 negative; Rectal; ER negative; PR negative; Her2-; HR-; ER-; PR-; HR negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Breast Diseases; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: 2020-013-00US3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No