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TP008/#1500  Trial in progress: phase 2/3 study of navtemadlin as maintenance therapy in patients with advanced or recurrent endometrial cancer who responded to chemotherapy (ENGOT-EN21; GOG-3089)
  1. Nicole Concin1,
  2. Ugo De Giorgi2,
  3. Toon Van Gorp3,4,
  4. Jérôme Alexandre5,
  5. Kristina Lindemann6,7,
  6. Christian Marth1,
  7. Regina Berger1,
  8. David Cibula8,
  9. Maria Quindos9,
  10. Alessandra Bologna10,
  11. Jacob Korach11,
  12. Christos Papadimitriou12,
  13. Shibani Nicum13,
  14. Dearbhaile Collins14,
  15. Reg Myers15,
  16. Wayne Rothbaum15,
  17. Thomas Herzog16,
  18. Bradley Monk17 and
  19. Noelle Gillette Cloven18
  1. 1Medical University of Innsbruck, Univ-Clinic for Gynecology and Obstetrics, Innsbruck, Austria and AGO (Arbeitsgemeinschaft für gynäkologische Onkologie), Gynaecology and Obstetrics, Innsbruck, Austria
  2. 2IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) ‘Dino Amadori’ and Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Group, Department of Medical Oncology, Meldola, Italy
  3. 3University Hospital Leuven, Leuven Cancer Institute, Department of Gynaecology and Obstetrics, Leuven, Belgium
  4. 4Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Department of Gynaecology and Obstetrics, Leuven, Belgium
  5. 5Université de Paris Cité, Hôpital Cochin, Medical Oncology, Paris, France
  6. 6Oslo University Hospital, The Norwegian Radium Hospital, Department of Gynaecologic Cancer, Oslo, Norway
  7. 7Institute of Clinical Medicine, University of Oslo and the Nordic Society of Gynaecological Oncology (NSGO) Group, Department of Gynaecologic Cancer, Oslo, Norway
  8. 8General University Hospital in Prague, First Faculty of Medicine, Charles University, Department of Obstetrics and Gynaecology, Prague, Czech Republic
  9. 9Complexo Hospitalario Universitario de A Coruña, Spanish Gynaecological Cancer Research Group (GEICO), Biomedical Research Institute (INIBIC), Medical Oncology Department, A Coruña, Spain
  10. 10Azienda Unità Sanitaria Locale di Reggio Emilia-IRCCS, Department of Oncology, Reggio Emilia, Italy
  11. 11Sheba Medical Center, Gynecology Oncology, Ramat Gan, Tel Aviv, Israel
  12. 12Aretaieion University Hospital, National and Kapodistrian University of Athens, Oncology Unit, Second Department of Surgery, Athens, Greece
  13. 13University College London, Research Department of Oncology, London, UK
  14. 14Cork University Hospital, Department of Medical Oncology, Cork, Ireland
  15. 15Kartos Therapeutics Inc., Clinical Sciences Department, Redwood City, USA
  16. 16University of Cincinnati Cancer Center, Obstetrics and Gynecology, Cincinnati, USA
  17. 17HonorHealth Research Institute, University of Arizona, Creighton University School of Medicine, Obstetrics and Gynecology, Phoenix, USA
  18. 18Texas Oncology-Fort Worth Cancer Center, Obstetrics and Gynecology, Fort Worth, USA


Introduction Advanced/recurrent endometrial cancer (EC) has poor prognosis with 5-year survival rate of ~17% (Colombo 2016; Siegel 2022). Maintenance treatment may extend the response to initial chemo/chemoimmunotherapy. Mouse double minute 2 (MDM2), a key negative regulator of p53, is upregulated in ~50% of EC patients (Jeczen 2007) due to loss of p14ARF, a critical modulator of intranuclear MDM2 levels, thus preventing p53 tumor suppressor function. Navtemadlin is a potent, selective MDM2 inhibitor that restores p53-mediated apoptosis in TP53 WTtumors. The sensitivity of EC to genotoxic chemotherapy (Miller 2020) suggests susceptibility to p53-mediated apoptosis. Post-chemotherapy maintenance with navtemadlin may provide a non-genotoxic way to maintain p53-driven activity and tumor cell control in the ~50% of TP53 WTEC patients (Nakamura 2019). KRT-232–118 is a Global 2-part Phase 2/3 study evaluating the safety and efficacy of navtemadlin maintenance therapy in TP53 WT advanced/recurrent EC patients following response to chemotherapy (EudraCT 2022–5002196-31; NCT05797831).

Methods Adults with ECOG PS 0–1 who completed up to 6 cycles of chemotherapy excluding adjuvant/neo-adjuvant therapy and achieved CR or PR (RECIST v1.1) are eligible. The open-label Phase 2 randomizes patients to oral navtemadlin at a dose of 180 mg or 240 mg QD (Day 1–7/28-day cycle), or observation; primary endpoint is recommended Phase 3 dose (RP3D). The double-blind Phase 3 will randomize patients (2:1) to the RP3D vs placebo QD (Day 1–7/28-day cycle); stratification is by response and disease stage. Primary endpoint for Phase 3 is PFS by blinded independent review.

Current Trial Status This study is now open to enrollment.

Abstract TP008/#1500 Figure 1

Study schema of KRT-232–118

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