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

Primary Purpose

Triple Negative Breast Cancer, Endometrial Cancer, Solid Tumor, Unspecified, Adult

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fruquintinib
Tislelizumab
Sponsored by
Hutchison Medipharma Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic ArizonaRecruiting
  • Highlands OncologyRecruiting
  • Beverly Hills Cancer CenterRecruiting
  • University of ColoradoRecruiting
  • Florida Cancer Specialists - FCS SouthRecruiting
  • Florida Cancer Center NorthRecruiting
  • Florida Cancer Specialists PanhandleRecruiting
  • Florida Cancer Specialists - East (FCS East)Recruiting
  • HOC AON Baton Rouge / Sarah CannonRecruiting
  • Messino Cancer CenterRecruiting
  • Oklahoma University Stephenson Cancer CenterRecruiting
  • Women and Infants Hospital of Rhode IslandRecruiting
  • Tennessee Oncology-ChattanoogaRecruiting
  • Tennesse OncologyRecruiting
  • Vanderbilt Ingram Cancer CenterRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1

Part 2

Arm Description

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

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

Outcomes

Primary Outcome Measures

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
Recommended Phase 2 Dose
To confirm the RP2D of fruquintinib in combination with tislelizumab
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

Secondary Outcome Measures

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

Full Information

First Posted
September 23, 2020
Last Updated
November 11, 2022
Sponsor
Hutchison Medipharma Limited
Collaborators
BeiGene
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1. Study Identification

Unique Protocol Identification Number
NCT04577963
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 9, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hutchison Medipharma Limited
Collaborators
BeiGene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
112 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1
Arm Type
Experimental
Arm Description
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
Arm Title
Part 2
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Fruquintinib
Other Intervention Name(s)
HMPL-013
Intervention Description
Oral VEGFR inhibitor
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
BGB-A317
Intervention Description
PD-1 inhibitor
Primary Outcome Measure Information:
Title
Adverse Events by type, frequency, and severity
Description
To assess the safety and tolerability by monitoring AEs characterized by type, frequency, severity per NCI-CTCAE v5.0
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Recommended Phase 2 Dose
Description
To confirm the RP2D of fruquintinib in combination with tislelizumab
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Objective Response Rate
Description
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
Time Frame
Up to 18 months
Secondary Outcome Measure Information:
Title
Maximum plasma concentrations of fruquintinib with blood sampling
Description
Blood samples will be taken to measure levels of fruquintinib
Time Frame
Up to 18 months
Title
Maximum serum concentrations of tislelizumab with blood sampling
Description
Blood samples will be taken to measure levels of tislelizumab
Time Frame
Up to 18 months
Title
Progression-free Survival
Description
To further evaluate efficacy of fruquintinib in combination with tislelizumab in patients with advanced or metastatic TNBC or EC per investigator assessment
Time Frame
Up to 24 months
Title
Changes from baseline in biomarkers
Description
To detect the expression biomarkers in tumor tissues of patients
Time Frame
Up to 18 months
Title
Incidence of ADA to tislelizumab
Description
To evaluate the immunogenicity of fruquintinib in combination with tislelizumab
Time Frame
Up to 18 months
Title
Disease Control Rate (DCR)
Description
The incidence of complete response, partial response, and stable disease
Time Frame
Up to 24 months
Title
Clinical Benefit Rate
Description
The incidence of partial response and stable disease
Time Frame
Up to 24 months
Title
Duration of Response
Description
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
Time Frame
Up to 24 months
Title
Overall Survival
Description
The period from date of enrollment to date of death
Time Frame
Up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alberto Fernandez
Phone
973-567-3891
Email
albertof@hutch-med.com
First Name & Middle Initial & Last Name or Official Title & Degree
Keneikia Morgan
Email
keneikiam@hutch-med.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Schelman, MD, PhD
Organizational Affiliation
Hutchison MediPharma International
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
855-776-0015
Facility Name
Highlands Oncology
City
Springdale
State/Province
Arkansas
ZIP/Postal Code
72762
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H Holtzen
Email
HHoltzen@hogonc.com
First Name & Middle Initial & Last Name & Degree
Thaddeus Beck, MD
Facility Name
Beverly Hills Cancer Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ali Muhammas
Email
AMuhammad@bhcancercenter.com
First Name & Middle Initial & Last Name & Degree
Linnea Chap, MD
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J Diamond
Email
MARK.MORROW@CUANSCHUTZ.EDU
First Name & Middle Initial & Last Name & Degree
Jennifer Diamond, MD
Facility Name
Florida Cancer Specialists - FCS South
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33980
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
V Wright-Browne
Email
browne@flcancer.com
First Name & Middle Initial & Last Name & Degree
Vance Wright-Browne, MD
Facility Name
Florida Cancer Center North
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33709
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
G Wright
First Name & Middle Initial & Last Name & Degree
Gail Wright, MD
Facility Name
Florida Cancer Specialists Panhandle
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
V Bhanderi
Email
vbhanderi@flcancer.com
First Name & Middle Initial & Last Name & Degree
Pareshkumar Patel, MD
Facility Name
Florida Cancer Specialists - East (FCS East)
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E Harris
First Name & Middle Initial & Last Name & Degree
Eric Harris, MD
Facility Name
HOC AON Baton Rouge / Sarah Cannon
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M Castine
Email
mcastine@gmail.com
First Name & Middle Initial & Last Name & Degree
Michael Castine, MD
Facility Name
Messino Cancer Center
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28806
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C Chay
First Name & Middle Initial & Last Name & Degree
Christopher Chay, MD
Facility Name
Oklahoma University Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susanna Ulahannan, MD
First Name & Middle Initial & Last Name & Degree
Susanna Ulahannan
Facility Name
Women and Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cara Mathews, MD
First Name & Middle Initial & Last Name & Degree
Cara Mathews
Facility Name
Tennessee Oncology-Chattanooga
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
B Daniel
Email
Nicole.Shoviak@SarahCannon.com
First Name & Middle Initial & Last Name & Degree
Brooke Daniel, MD
Facility Name
Tennesse Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E Hamilton
First Name & Middle Initial & Last Name & Degree
Erika Hamilton, MD
Facility Name
Vanderbilt Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cathy Eng, MD
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H Garber
Email
dtripathy@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Haven Garber, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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