(P 416) A PHASE 2 MULTICENTER OPEN-LABEL BASKET STUDY OF TAZEMETOSTAT IN ADULT PATIENTS WITH INI1-NEGATIVE EPITHELIOID SARCOMA – FINAL ANALYSIS

Author(s)

Mrinal M. Gounder, MD

Associate Attending Physician
Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College
New York, New York, United States

Co-Author(s)

Patrick Schöffski, MD, MPH

Head
General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute
Leuven, Vlaams-Brabant, Belgium
Robin L. Jones, BSc, MB BS, Royal Physician MRCP, MD

Professor
Medical Oncology, The Royal Marsden and Institute of Cancer Research
London, England, United Kingdom
MA

Mark Agulnik, MD

Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
Chicago, Illinois, United States
Gregory M. Cote, MD PhD (he/him/his)

Associate Professor of Medicine
Mass General Cancer Center, Massachusetts General Hospital
Boston, Massachusetts, United States
Steven Attia, DO

Consultant
Mayo Clinic in Florida, Jacksonville, FL, USA
Jacksonville, Florida, United States
Rashmi Chugh, MD

Professor of Internal Medicine
University of Michigan Rogel Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Tom Wei-Wu W. Chen, MD, PhD

Attending physician
National Taiwan University Cancer Center and National Taiwan University, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)
TJ

Thierry Jahan, MD

University of California San Francisco, San Francisco, CA, USA
San Francisco, California, United States
Elizabeth T. Loggers, MD, PhD (she/her/hers)

Professor
Fred Hutchinson Cancer Center
Seattle, Washington, United States
Abha A. Gupta, MD (she/her/hers)

Dr.
The Hospital for Sick Children and Princess Margaret Cancer Center, Toronto, ON, Canada
Toronto, Ontario, Canada
Antoine Italiano, N/A, MD, PhD

Head
Department of Medicine, Institut Bergonié
Bordeaux, Aquitaine, France
George D. D. Demetri, MD (he/him/his)

Senior Vice President for Experimental Therapeutics
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Ravin Ratan, MD, M.Ed.

Associate Professor
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Lara E. Davis, MD

Sarcoma Program Director
Knight Cancer Institute, Oregon Health & Science University
Portland, Oregon, United States
OM

Olivier Mir, MD, PhD

Institut Gustave-Roussy, Villejuif, France
Villejuif, Ile-de-France, France
Palma Dileo, MD (she/her/hers)

Consutant Medical Oncologist
IRCCS Istituto Ortopedico Rizzoli
Bologna, Emilia-Romagna, Italy
Brian A. Van Tine, MD, PhD

Professor of Medicine
Washington University in St Louis School of Medicine
St. Louis, Missouri, United States
Joseph G. Pressey, MD

Professor of Pediatrics
University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Cincinnati, Ohio, United States
RB

Rajat Bannerji, MD, PhD

Ipsen, Cambridge, MA, USA
Cambridge, Massachusetts, United States
YC

Yingxue Chen, PhD

Ipsen, Cambridge, MA, USA
Cambridge, Massachusetts, United States
JL

Jia Li, MD

Ipsen, Cambridge, MA, USA
Cambridge, Massachusetts, United States
AS

Attila Szanto, PhD

Ipsen, Cambridge, MA, USA
Cambridge, Massachusetts, United States
Silvia Stacchiotti, MD

Medical Oncologist
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardia, Italy

Objective: To report the clinical activity and safety of the EZH2 inhibitor tazemetostat (Taz) in patients (pts) with INI1-negative epithelioid sarcoma (INI1-neg ES) (NCT02601950).

Methods: Eligible pts with locally advanced or metastatic INI1-neg ES were enrolled into cohorts 5 (C5) or 6 (C6; plus paired tumor biopsies). Pts received oral Taz 800 mg BID in continuous 28-day cycles. Primary endpoint: investigator-assessed objective response rate (ORR) (RECIST v1.1). Secondary endpoints: duration of response (DOR), 32-week disease control rate (DCR), progression-free survival (PFS), overall survival (OS). Activity and safety were assessed in pts receiving ≥1 Taz dose.

Results: From 22 Dec 2015 to 30 Aug 2021, 131 enrolled pts received Taz (C5, n=62; C6, n=69). Median age, 37.0 (range 16–88) yrs; male, 63%; had progressive disease at study entry, 97%. Median exposure duration was 5.1 (range 0.1–69.0) mths (C5, 5.5 mths; C6, 4.2 mths). Clinical activity in C5 was previously published (Gounder M et al. 2020 The Lancet); C6 showed confirmatory outcomes (Table). Exposure–efficacy analyses indicated numerical trends of higher ORR and DCR and longer DOR with higher Taz exposure (>median AUC of 3314 µg·day/mL) vs lower than median exposure. Grade 3–4 treatment-related adverse events (TRAE) occurred in 12% of pts, grade 3–4 treatment-emergent adverse events (TEAEs) in 42%, serious TRAEs in 2%, and serious TEAEs in 34%. TEAEs led to dose reduction in 3% of pts, Taz withdrawal in 4%, and study discontinuation in 12%. Most common TRAEs were nausea, fatigue, diarrhea and decreased appetite. No new safety findings reported.

Conclusion: A notable proportion of pts with advanced/progressive INI-neg ES had durable responses to Taz, which was generally well tolerated (low TRAEs, dose reduction and discontinuation rates), and positive exposure–efficacy relationships were identified. These findings support further studies of Taz in pts with epithelioid sarcoma.

Clinical outcomes in C5 and C6
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