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

Study Overview
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Brief Summary
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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)

Official Title
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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

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

Intervention / Treatment
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* Drug: Fruquintinib
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>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<br>* Oral VEGFR inhibitor<br>* Other names: HMPL-013;Drug: Tislelizumab<br>* PD-1 inhibitor<br>* Other names: BGB-A317;|
| Experimental: Part 2<br>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<br>* Oral VEGFR inhibitor<br>* Other names: HMPL-013;Drug: Tislelizumab<br>* PD-1 inhibitor<br>* Other names: BGB-A317;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ER negative, Colon, Rectal, Breast cancer, Triple negative, Her2-, HR-, ER-, PR-, Her2 negative, HR negative, PR negative, TNBC, VEGF, VEGFR, Endometrial cancer, mCRC, Colorectal