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

Sponsor
Hutchison Medipharma Limited (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04577963
Collaborator
BeiGene (Industry)
112
Enrollment
18
Locations
2
Arms
30.7
Anticipated Duration (Months)
6.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
112 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 9, 2021
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    3. 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

    1. Maximum plasma concentrations of fruquintinib with blood sampling [Up to 18 months]

      Blood samples will be taken to measure levels of fruquintinib

    2. Maximum serum concentrations of tislelizumab with blood sampling [Up to 18 months]

      Blood samples will be taken to measure levels of tislelizumab

    3. 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

    4. Changes from baseline in biomarkers [Up to 18 months]

      To detect the expression biomarkers in tumor tissues of patients

    5. Incidence of ADA to tislelizumab [Up to 18 months]

      To evaluate the immunogenicity of fruquintinib in combination with tislelizumab

    6. Disease Control Rate (DCR) [Up to 24 months]

      The incidence of complete response, partial response, and stable disease

    7. Clinical Benefit Rate [Up to 24 months]

      The incidence of partial response and stable disease

    8. 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

    9. Overall Survival [Up to 36 months]

      The period from date of enrollment to date of death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Arizona Phoenix Arizona United States 85054
    2 Highlands Oncology Springdale Arkansas United States 72762
    3 Beverly Hills Cancer Center Beverly Hills California United States 90211
    4 University of Colorado Aurora Colorado United States 80045
    5 Florida Cancer Specialists - FCS South Port Charlotte Florida United States 33980
    6 Florida Cancer Center North Saint Petersburg Florida United States 33709
    7 Florida Cancer Specialists Panhandle Tallahassee Florida United States 32308
    8 Florida Cancer Specialists - East (FCS East) West Palm Beach Florida United States 33401
    9 Indiana University Health Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    10 HOC AON Baton Rouge / Sarah Cannon Baton Rouge Louisiana United States 70809
    11 Summit Health NJ Florham Park New Jersey United States 07932
    12 Mission Hospital Cancer Center Asheville North Carolina United States 28806
    13 Oklahoma University Stephenson Cancer Center Oklahoma City Oklahoma United States 73104
    14 Women and Infants Hospital of Rhode Island Providence Rhode Island United States 02905
    15 Tennessee Oncology-Chattanooga Chattanooga Tennessee United States 37404
    16 Tennesse Oncology Nashville Tennessee United States 37203
    17 Vanderbilt Ingram Cancer Center Nashville Tennessee United States 37232
    18 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Hutchison Medipharma Limited
    • BeiGene

    Investigators

    • Study Director: William Schelman, MD, PhD, Hutchison MediPharma International

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hutchison Medipharma Limited
    ClinicalTrials.gov Identifier:
    NCT04577963
    Other Study ID Numbers:
    • 2020-013-00US3
    First Posted:
    Oct 8, 2020
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Hutchison Medipharma Limited
    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
    Additional relevant MeSH terms:
    Endometrial Neoplasms
    Triple Negative Breast Neoplasms

    Study Results

    No Results Posted as of Jul 28, 2022