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

NCT04577963 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 2020-013-00US3
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 16

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)

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

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of Patients With Dose-Limiting Toxicities (DLTs)

  According to National Cancer Institute Common Terminology Criteria for Adverse Events(AEs) v5.0, DLT was defined as any 1 of following toxicities during DLT assessment window and considered by Investigator to be related to 1 or more study treatments:a)Hematologic: grade(G) 4 neutropenia lasting \>7 days, G ≥3 febrile neutropenia, G 3 thrombocytopenia with clinically significant bleeding, G 4 thrombocytopenia, G ≥4 anemia.b) Non-hematologic:all G ≥3 non-hematologic toxicities except:G 3 endocrinopathy controlled by hormonal replacement with no hospitalization and resolved to G ≤1 within 7 days, G 3 nausea/vomiting or diarrhea for \<72 hours with antiemetic and supportive care, G 3 fatigue for \<1 week, G ≥3 electrolyte abnormality lasting up to 72 hours and resolving with treatment, G 3 rash returning to baseline or G ≤1 within 7 days with treatment,G ≥3 amylase or lipase elevation without symptoms of pancreatitis,G 3 hypertension returning to baseline or G≤1 within 7 days with treatment.

  From the first dose of study treatment (Day 1) up to Day 28 of Cycle 1 (cycle duration: 4 weeks)

• Part 1: Recommended Phase 2 Dose (RP2D) of Fruquintinib in Combination With Tislelizumab

  The RP2D of fruquintinib in combination with tislelizumab based on the safety and tolerability assessments in Part 1 patients.

  From the first dose of study treatment (Day 1) up to Day 28 of Cycle 1 (cycle duration: 4 weeks)

• Part 2: Objective Response Rate (ORR)

  The ORR was defined as the percentage of patients with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator using RECIST v1.1. The BOR was defined as the best response recorded from the start of study treatment until documented RECIST v1.1 progression or the start date of new anticancer therapy, whichever came first. The CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had a reduction in short axis to \<10 millimeters (mm). The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months

Secondary Outcomes (11)

• Part 1: Objective Response Rate

  Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months

• Parts 1 and 2: Progression-free Survival (PFS)

  Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months

• Parts 1 and 2: Disease Control Rate (DCR)

  Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months

• Parts 1 and 2: Clinical Benefit Rate (CBR)

  Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months

• Parts 1 and 2: Duration of Response (DoR)

  Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months

Study Arms (2)

Part 1

EXPERIMENTAL

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; Drug: Tislelizumab

Part 2

EXPERIMENTAL

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; Drug: Tislelizumab

Interventions

Fruquintinib DRUG

Oral VEGFR inhibitor

Also known as: HMPL-013

Part 1; Part 2

Tislelizumab DRUG

PD-1 inhibitor

Also known as: BGB-A317

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hutchmed: lead
• BeiGene: collaborator

Study Sites (16)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Highlands Oncology

Springdale, Arkansas, 72762, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists - FCS South

Port Charlotte, Florida, 33980, United States

Location

Florida Cancer Center North

St. Petersburg, Florida, 33709, United States

Location

Florida Cancer Specialists Panhandle

Tallahassee, Florida, 32308, United States

Location

Florida Cancer Specialists - East (FCS East)

West Palm Beach, Florida, 33401, United States

Location

HOC AON Baton Rouge / Sarah Cannon

Baton Rouge, Louisiana, 70809, United States

Location

Messino Cancer Center

Asheville, North Carolina, 28806, United States

Location

Oklahoma University Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Tennessee Oncology-Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennesse Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Endometrial Neoplasms; Colorectal Neoplasms; Breast Neoplasms

Interventions

HMPL-013; tislelizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Limitations and Caveats

The study was terminated early based upon the strategic evaluation of clinical development of fruquintinib in the United States. This change was not based on any concern for patient safety or efficacy relative to fruquintinib and/or tislelizumab treatment.

Results Point of Contact

• Title: William Schelman, MD, PhD, Senior Vice President, Clinical Development, US/Europe
• Organization: HUTCHMED International, Inc.

williams@hutch-med.com

+1 9733064490

Study Officials

• William Schelman, MD, PhD

  HUTCHMED International

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: October 8, 2020
• Study Start: August 9, 2021
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: July 14, 2025
• Results First Posted: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)