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Scientific Publications | 17 Sep 2021

ESMO2021: A Phase Ib/II Study of Fruquintinib in Combination with Tislelizumab in Patients with Advanced Triple Negative Breast Cancer

Title: An open-label, phase Ib/II study to evaluate the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced triple negative breast cancer
Lead Author: Debu Tripathy, MD, The University of Texas MD Anderson Cancer Center
Session: ePoster
Presentation Number: 337TiP

 

Background

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in triple-negative breast cancer (TNBC), but many patients (pts) do not respond to ICIs or will develop resistance. Combining VEGFR inhibition may potentiate ICI efficacy by normalizing vascular immune crosstalk and improving immune effector cell infiltration. Tislelizumab (T) is a humanized, IgG4-variant monoclonal antibody against PD-1. Fruquintinib (F) is a novel, highly selective, oral, tyrosine kinase inhibitor of VEGFR-1, 2, 3. Safety and preliminary efficacy of F were demonstrated in metastatic breast cancer, including TNBC, in a phase 1 study in China (2009-013-00CH1) and in an ongoing phase 1/1b study in the US (2015-013-00US1). We hypothesize that the addition of F can potentially overcome resistance to ICI and improve TNBC activity.

 

Trial design

This is an open-label, phase 1b/2 study (NCT04579757) to assess the safety, PK and efficacy of F in combination with T in pts with locally advanced or metastatic TNBC independent of PD-L1 status, including both immunotherapy (IO) pre-treated and naïve pts. Pts must have progressed on 1-3 cytotoxic chemotherapies, have ECOG performance status 0 or 1, and an expected survival ≥12 weeks. The study consists of a safety lead-in (Part 1) and dose expansion phase (Part 2). The primary objective of Part 1 is to assess safety and tolerability and confirm the RP2D of F in combination with T. Safety will be assessed via dose limiting toxicities, treatment emergent adverse events, electrocardiograms, clinical lab abnormalities, and vital signs. The primary objective of Part 2 is to estimate the objective response rate (ORR) of F in combination with T per RECIST v1.1. Part 2 will include 2 expansion cohorts of ∼30 pts each: Cohort A: IO-treated; and B: IO-naïve. Demographics, efficacy, safety, and PK will be summarized using descriptive statistics. Antitumor activity, based on investigator-assessed overall response, and ORR will be calculated using the Clopper-Pearson method. Time to event variables will be summarized descriptively using the Kaplan-Meier method. No statistical hypothesis testing is planned.

 

Clinical trial identification

NCT04579757.

 

Editorial acknowledgement

Writing assistance was provided by Amy C. Porter, Ph.D. of Synchrogenix, LLC, a Certara Company, on behalf of HUTCHMED Internataional Corporation.

 

Legal entity responsible for the study

HUTCHMED International Corporation.

 

Funding

HUTCHMED International Corporation.

 

Disclosure

D. Tripathy: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Polyphor; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Exact Sciences; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: OncoPep; Financial Interests, Personal, Advisory Role: Immunomedics. S.M. Ukrainskyj: Financial Interests, Personal, Full or part-time Employment: HUTCHMED International Corporation; Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Full or part-time Employment: Celgene. Z. Yang: Financial Interests, Personal, Full or part-time Employment: HUTCHMED International Corporation. M. Kania: Financial Interests, Personal, Full or part-time Employment: HUTCHMED International Corporation; Financial Interests, Personal, Stocks/Shares: HUTCHMED International Corporation; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Personal, Other, Travel expenses: HUTCHMED International Corporation. W. Schelman: Financial Interests, Personal, Stocks/Shares: HUTCHMED International Corporation; Financial Interests, Personal, Full or part-time Employment: HUTCHMED International Corporation. E. Hamilton: Financial Interests, Institutional, Funding: OncoMed, Genentech/Roche, Zymeworks, Rgenix, ArQule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Torque, Black Diamond, Karyopharm, Infinity Pharmaceuticals, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomed; Financial Interests, Institutional, Advisory Role: Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen.