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PR088/#198  EZH2/EZH1 inhibitor tulmimetostat (CPI-0209): preliminary phase II results and first biomarker findings in patients with arid1a-mutant ovarian clear cell or endometrial carcinomas (OCCC/EC)
  1. Charles Drescher1,
  2. Harriet Walter2,
  3. Elvire Pons-Tostivint3,
  4. Nehal Lakhani4,
  5. Vincent Ribrag5,
  6. Martin Gutierrez6,
  7. Ryan Sullivan7,
  8. Donald Harvey8,
  9. Kalyan Banda9,
  10. Michal Kwiatek10,
  11. Alejandro Garcia-Sancho11,
  12. Linda Duska12,
  13. Pier Luigi Zinzani13,
  14. Anjali Thakur14,
  15. Lennart Kann14,
  16. Rainer Boxhammer14,
  17. Nicola Faulhaber14,
  18. Julia Jauch-Lembach14 and
  19. Hedy Kindler15
  1. 1Swedish Cancer Institute, -, Seattle, USA
  2. 2University of Leicester and University Hospitals of Leicester NHS Trust, -, Leicester, UK
  3. 3Medical Oncology, University Hospital Nantes, Nantes, France
  4. 4START Midwest, -, Grand Rapids, USA
  5. 5Centre de Lutte Contre le Cancer (CLCC), Gustave Roussy (institut De Cancerologie Gustave-roussy), Villejuif, France
  6. 6Hackensack University Medical Center, -, Hackensack, USA
  7. 7Massachusetts General Hospital, -, Boston, USA
  8. 8Emory University School of Medicine and Winship Cancer Institute, -, Atlanta, USA
  9. 9Fred Hutchinson Cancer Center, -, Seattle, USA
  10. 10Centrum Medyczne Pratia Poznań, -, Skorzewo, Poland
  11. 11Hospital Universitario de Salamanca, Ibsal, Salamanca, Spain
  12. 12University of Virginia, -, Charlottesville, USA
  13. 13IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia ‘Seràgnoli’ and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, -, Bologna, Italy
  14. 14MorphoSys AG, -, Planegg, Germany
  15. 15University of Chicago, -, Chicago, USA


Introduction ARID1A mutation (ARID1Amut) has a high incidence in OCCC (up to 60%) and EC (up to 40%), with evidence as a negative prognostic marker for treatment resistance and outcomes. EZH2 inhibition in ARID1Amut solid tumors results in tumor growth inhibition (Bitler et al. Nat Med 2015;21:231–238). Preliminary Phase II (NCT04104776) efficacy, safety, and biomarker findings from OCCC and EC cohorts receiving tulmimetostat are reported.

Methods The Phase II study is evaluating tulmimetostat 350 mg once daily in 6 disease-based cohorts, including ARID1Amut OCCC/EC. Per Simon 2-stage design, expansion of enrolment (plus n=19 patients per cohort in Stage 2) requires objective response rate (ORR) ≥1/10 in Stage 1. Primary endpoint is ORR; secondary endpoints include safety. Evaluation of two additional dose levels was implemented for both cohorts, per FDA recommendation of Project Optimus, to inform on optimal tulmimetostat dose.

Results 24 patients were enrolled (OCCC, n=14; EC, n=10); 50% of each cohort have received ≥3 prior treatment lines. Both cohorts are eligible for Stage 2 expansion, with 1 and 2 confirmed partial responses in patients with OCCC and EC, respectively (table 1). The manageable safety profile across all 6 tumor cohorts (n=81) was consistent with known class effects; Grade ≥3 related adverse events (≥10% of patients) included thrombocytopenia, anemia, neutropenia, and diarrhea. Next generation sequencing did not reveal a specific hotspot for ARID1Amut locations impacting clinical outcome in patients with OCCC/EC.

Conclusion/Implications These preliminary findings in heavily pre-treated patients with ARID1Amut OCCC/EC support continued investigation of tulmimetostat monotherapy.

Abstract PR088/#198 Table 1

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