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2022-RA-459-ESGO UPLIFT (ENGOT-ov67/GOG-3048) a registrational trial of Upifitamab Rilsodotin (XMT-1536; UpRi), a NaPi2b-directed antibody drug conjugate (ADC) in platinum-resistant ovarian cancer
  1. Nicole Concin1,
  2. Bradley J Monk2,
  3. Mansoor Raza Mirza3,
  4. Robert L Coleman4,
  5. Isabelle Ray-Coquard5,
  6. Bhavana Pothuri6,
  7. Jean-Francois Baurain7,
  8. J Alejandro Perez-Fidalgo8,
  9. David Cibula9,
  10. Antonella Saverse10,
  11. Susana Banerjee11,
  12. Radek Madry12,
  13. Christian Marth13,
  14. Emily Putiri14,
  15. Jamie Barrett14,
  16. Leslie DeMars14 and
  17. Debra Richardson15
  1. 1Evangelische Kliniken Essen-Mitte, Essen, Germany
  2. 2University of Arizona College of Medicine, Tucson, AZ
  3. 3Rigshospitalet – University Hospital Copenhagen, Copenhagen, Denmark
  4. 4US Oncology, The Woodlands, TX
  5. 5Leon Berard Center, Lyon, France
  6. 6NYU Langhone Medical Center, New York, NY
  7. 7Saint Luc University Hospital, Brussels, Belgium
  8. 8University Clinical Hospital of Valencia, Valencia, Spain
  9. 9General University Hospital in Prague, Prague, Czech Republic
  10. 10National Cancer Institute Regina Elena, IRCCS, Rome, Italy
  11. 11Royal Marsden Hospital – London, London, UK
  12. 12Heliodor Swiecicki Clinical Hospital at the Karol Marcinkowski Medical University, Poznan, Poland
  13. 13University Hospital Innsbruck – Tyrolean Hospital, Innsbruck, Austria
  14. 14Mersana Therapeutics, Cambridge, MA
  15. 15Stephenson Cancer Centre-University of Oklahoma, Oklahoma City, OK


Introduction/Background UpRi is a first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous epithelial ovarian, fallopian tube and primary peritoneal cancers (HGSOC), with limited expression in healthy tissues. Preliminary antitumor activity from the Phase 1b expansion cohort of heavily pretreated patients with recurrent HGSOC has been reported (Richardson et al., SGO 2022). These data suggested clinically meaningful activity in patients, notably in those with NaPi2b-high tumors (TPS≥75). Effective and well-tolerated treatments for platinum-resistant ovarian cancer (PROC) remain a substantial unmet medical need. The standard of care, single agent chemotherapy, has limited efficacy, significant toxicities, and short duration of response. UPLIFT was designed as a single-arm Ph2 registrational trial for UpRi monotherapy in PROC.

Methodology UPLIFT is enrolling patients with platinum-resistant HGSOC with up to 4 prior lines of therapy (LoT). Prior bevacizumab is required for patients with 1–2 prior LoT only; it is not required for patients with 3–4 prior LoT. Patients may enroll regardless of NaPi2b expression; ≤ Grade 2 peripheral neuropathy is permitted. Primary platinum refractory patients are excluded. UPLIFT will enroll ~180 patients globally, including approximately 100 patients with NaPi2b-high expression. UpRi will be dosed intravenously at 36 mg/m2 up to ~80 mg dose maximum every 4 weeks. Baseline tumor samples (fresh or archived) will be collected for central analysis of NaPi2b expression. Based on data from the Ph1b expansion cohort, the cut-off for high NaPi2b expression is Tumor Proportion Score (TPS) ≥75. The primary endpoint is ORR in NaPi2b-high expressing patients. Secondary endpoints include ORR in the overall population, duration of response, and safety. UPLIFT is being conducted in collaboration with ENGOT (ENGOT-ov67) and GOG (GOG-3048). NCT03319628

Results N/A trial in progress

Conclusion N/A trial in progress

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