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#168 UPLIFT (ENGOT-Ov67/GOG-3048): results from the phase 2 trial of upifitamab rilsodotin (UpRi; XMT-1536), a NaPi2b-directed dolaflexin antibody-drug conjugate (ADC) in platinum-resistant ovarian cancer (PROC)
  1. Nicole Concin1,
  2. John L Hays2,
  3. Alejandro Pérez Fidalgo3,
  4. Bhavana Pothuri4,
  5. Susana N Banerjee5,
  6. Sharad Ghamande6,
  7. Isabelle Ray-Coquard7,
  8. Anna Germanova8,
  9. Bobbie J Rimel9,
  10. Domenica Lorusso10,
  11. Noelle G Cloven11,
  12. Jean-Francois Baurain12,
  13. Leslie M Randall13,
  14. Birute Brasiuniene14,
  15. Jill H Tseng15,
  16. Dagmara Klasa-Mazurkiewicz16,
  17. Theresa L Werner17,
  18. Ana Oaknin18,
  19. Joo Ern Ang19,
  20. Alexandra Leary20,
  21. Erin Bishop21,
  22. Christian Marth22,
  23. Chelsea Bradshaw23,
  24. Robert A Burger23,
  25. Antonio Gonzalez-Martin24 and
  26. Debra L Richardson25
  1. 1Ev. Kliniken Essen-Mitte, Essen, Germany
  2. 2Wexner Medical Center and James Cancer Hospital, Ohio State University, Columbus, Oh, USA
  3. 3Hospital Clinico Universitario de Valencia. INCLIVA. CIBERONC, Valencia, Spain
  4. 4Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, USA
  5. 5The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, National Cancer Research Institute (NCRI), London, UK
  6. 6Georgia Cancer Center, Augusta University, Augusta, Ga, USA
  7. 7Centre Léon Bérard, Lyon, France
  8. 8Charles University in Prague, Prague, Czech Republic
  9. 9Cedars Sinai Medical Center, Los Angeles, Ca, USA
  10. 10Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  11. 11Texas Oncology-Fort Worth Cancer Center, Fort Worth, Tx, USA
  12. 12Cliniques universitaires Saint-Luc, Bruxelles, Belgium
  13. 13Massey Comprehensive Cancer Center, VCUHealth, Richmond, Va, USA
  14. 14National Cancer Institute of Lithuania, Vilnius University, Vilnius, Lithuania
  15. 15UC Irvine Health, Orange County, Ca, USA
  16. 16Medical University of Gdansk, Gdansk, Poland
  17. 17Huntsman Cancer Institute, University of Utah, Salt Lake City, Ut, USA
  18. 18Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
  19. 19Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  20. 20Cancer Medicine department, Institut de Cancérologie Gustave Roussy, Villejuif, France
  21. 21Medical College of Wisconsin, Milwaukee, Wi, USA
  22. 22Medical University Innsbruck, Innsbruck, Austria
  23. 23Mersana Therapeutics, Cambridge, Ma, USA
  24. 24Cancer Center Clinica Universidad de Navarra, Madrid, Spain
  25. 25Gynecologic Oncology, Stephenson Cancer Center/University of Oklahoma Health Sciences Center and Sarah Cannon Research Institute, Oklahoma City, Ok, USA


Introduction/Background Effective and well-tolerated treatments for PROC remain an unmet medical need; standard of care single agent chemotherapy has limited efficacy, with response rates at ~12%. Upifitamab rilsodotin (UpRi) is a Dolaflexin, high Drug-to-Antibody Ratio ADC targeting NaPi2b, a sodium-dependent phosphate transporter broadly expressed in high-grade serous epithelial ovarian cancer, with limited expression in normal tissues. UPLIFT was a single-arm Ph2 trial evaluating the efficacy and safety of UpRi in PROC.

Methodology UPLIFT enrolled patients with up to 4 prior lines of therapy; patients were dosed at 36mg/m2 Q4W. Patients enrolled regardless of NaPi2b expression; baseline tumor samples were collected to determine NaPi2b expression retrospectively. Primary endpoint was confirmed ORR in the NaPi2b-positive population. Secondary endpoints included ORR in the overall population, duration of response (DOR), and safety.

Results 268 patients were enrolled, 141 (53%) were determined to be NaPi2b-positive [TPS≥75]. The median prior lines of therapy among all patients was three; 31% received four prior lines of systemic treatment, 53% received at least one prior treatment for PROC. Additionally, 84% of patients received prior bevacizumab, 69% received prior PARPi. Based on data cut (May 31, 2023) investigator assessed confirmed ORR in the NaPi2b-positive population was 15.6% (95% CI, 10, 22.7); median DOR 7.4 months (95% CI, 4.2, NR). In the overall patient population, ORR was 13.1% (95% CI, 9.3, 17.7), DOR 7.4 months (95% CI, 3.6, 10.4). Dose reductions and discontinuations due to TRAE were 25% and 18.7%, respectively. The most frequently reported TRAEs were AST increase (69%), nausea (51.9%), thrombocytopenia/platelet count decrease (49.6%), fatigue (44%), anemia (39.2%) and pyrexia (37.7%). ILD/pneumonitis reported in 9.7% (Gr3 0.7%). Serious treatment emergent bleeding events were observed, including five G5 events.

Conclusion In this single-arm open label trial, ORR in the NaPi2b-positive and overall population did not show meaningful improvement compared to historical single-agent chemotherapy, though durable responses were observed.

Disclosures This trial was sponsored by Mersana Therapeutics, Inc.

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