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: Terminated
• Conditions: Colorectal Cancer; Triple Negative Breast Cancer; Endometrial Cancer; Solid Tumor, Unspecified, Adult
• Intervention / Treatment: Drug: Fruquintinib; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 52
• 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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Objective Response Rate	The ORR was defined as the percentage of patients with a confirmed BOR of CR or 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 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
Parts 1 and 2: Progression-free Survival (PFS)	PFS was defined as the time from the start of study treatment until the first radiographic documentation of objective progression as assessed by the investigator using RECIST v1.1, or death from any cause. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.	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)	The DCR was defined as the percentage of patients with a BOR of CR, PR, or stable disease (SD) lasting for at least 7 weeks 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 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. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study.	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)	The CBR was defined as the percentage of patients with a BOR of CR, PR, or durable SD (i.e., lasting for at least 6 months) as determined by the investigator using RECIST v1.1. Durable SD was SD for at least 6 months. 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 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. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study.	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)	The DoR was defined as the time from the first occurrence of PR or CR by RECIST v1.1, whichever came first until PD or death. 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 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. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum also demonstrated an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.	Tumor assessments performed every 8 weeks (+/-1 week) until PD, up to a maximum of approximately 34 months
Parts 1 and 2: Overall Survival (OS)	The OS was defined as the time from start of study treatment until the date of death due to any cause.	From the first dose of study treatment (Day 1) up to date of death due to any cause, up to a maximum of approximately 34 months
Parts 1 and 2: Plasma Concentrations of Fruquintinib and Metabolite M11	Blood samples were collected at the specified timepoints to determine plasma concentrations of fruquintinib and metabolite M11.	Pre-dose on Days 1, 8, 15, 21 of Cycle 1 and on Day 1 of Cycles 2, 4, 7, 13; 2 to 4 hours post-dose on Days 1 and 21 of Cycle 1 (cycle duration: 4 weeks)
Parts 1 and 2: Serum Concentrations of Tislelizumab	Blood samples were collected at the specified timepoints to determine serum concentrations of tislelizumab.	Pre-infusion on Day 1 of Cycles 1, 2, 4, 7, 13; at end of infusion on Day 1 of Cycles 1 and 4; on Days 8, 15, and 21 of Cycle 1 (cycle duration: 4 weeks)
Parts 1 and 2: Number of Patients With Antidrug Antibodies (ADAs) to Tislelizumab	Blood samples were collected at the specified timepoints to detect ADAs to tislelizumab. Treatment-induced ADA was defined as ADA negative at baseline and ADA positive post-baseline. Treatment-boosted ADA was defined as ADA positive at baseline that was boosted to a 4-fold or higher-level following treatment administration.	From the first dose of study treatment (Day 1) up to end of treatment, up to approximately 17 months for Part 1 and 20 months for Part 2
Part 2: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and TEAEs Leading to Treatment Discontinuation	An AE was any untoward medical occurrence in a clinical study patient temporally associated with the use of a study treatment, whether or not considered related to the treatment. An AE was considered "serious" if, in the view of either the investigator or sponsor, it resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, was a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was an abnormal pregnancy outcome in a child born to a female patient/female partner of a male patient exposed to study treatment or was an important medical event. TEAEs were AEs that started or worsened in severity on or after the first dose of study treatment and up to 30 days after the date of last study treatment administration.	From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 21 months
Part 2: Change From Baseline in Programmed Death-Ligand 1 (PD-L1) Expression	Expression of PD-L1 biomarker was planned to be assessed in tumor tissues of the patients. Baseline was defined as the last non-missing assessment prior to the first administration of any study treatment (whichever occurred first), including scheduled and unscheduled visits, unless otherwise specified.	Baseline (Day 1) up to end of treatment, up to approximately 20 months

Collaborators and Investigators

• Sponsor: Hutchmed
• Collaborators: BeiGene
• Investigators: Study Director: William Schelman, MD, PhD, HUTCHMED International

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Actual): June 18, 2024
• Study Completion (Actual): June 18, 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 (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

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: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Uterine Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Endometrial Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; 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
• product manufactured in and exported from the U.S.: No