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TP021/#1540  Reframe-O1/ENGOT-OV79/GOG-3086: a phase 2/3 open-label study evaluating the efficacy and safety of luveltamab tazevibulin versus investigator’s choice chemotherapy in relapsed platinum-resistant EOC expressing folate receptor-alpha
  1. R Wendel Naumann1,
  2. Antonio González-Martín2,
  3. Thomas Herzog3,
  4. Robert Coleman4,
  5. Isabelle Ray-Coquard5,
  6. Rowan Miller6,
  7. Lin Lu7,
  8. Hatem Dokainish8,
  9. Craig Berman9 and
  10. Ana Oaknin10
  1. 1Levine Cancer Institute, Carolinas Medical Center, Gynecologic Oncology, Charlotte, USA
  2. 2Clínica Universidad de Navarra, Medical Oncology, Madrid, Spain
  3. 3University of Cincinnati Cancer Center, Obstetrics and Gynecology, Cincinnati, USA
  4. 4US Oncology Research, Gynecologic Oncology, The Woodlands, USA
  5. 5CENTRE LEON BERARD, Oncology, LYON, France
  6. 6University College London, St Bartholomew’s Hospitals, Gynaecological Oncology, London, UK
  7. 7Sutro Biopharma, Biometrics, SSF, USA
  8. 8Sutro Biopharma, Clinical Science, SSF, USA
  9. 9Sutro Biopharma, Clinical Development, SSF, USA
  10. 10Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Gynaecologic Cancer Programme, Barcelona, Spain


Introduction Folate receptor alpha (FolRα) is a validated target in the treatment of platinum resistant ovarian cancer (PROC) expressing high-FolRα. There remains a high unmet need to treat PROC with low to moderate FolRα expression. Luveltamab tazevibulin (luvelta), a novel FolRα-targeting ADC with a hemiasterlin warhead (DAR4), is designed using site-specific conjugation technology to target a broad range of FolRα-expressing cancers. Luvelta demonstrated preliminary efficacy data (ORR of 37.5%; mDOR of 5.5 months; mPFS of 6.1 months) in 32 patients with advanced/relapsed EOC with FolRα expression of >25% (any intensity) in a Ph1 study (NCT03748186). ORR was higher at 5.2 mg/kg (43.8% versus 31.3%, n=32) compared to 4.3 mg/kg. Luvelta showed a manageable safety profile, with the most common grade 3+ adverse events of neutropenia, arthralgia, and anemia. This data forms the basis for a pivotal study of luvelta in patients with PROC with broad FolRα expression levels.

Methods REFRaME-O1/ENGOT-Ov79/GOG-3086 is a 2-part Phase 2/3 study of luvelta in subjects with relapsed PROC expressing FolRα. Part 1 is the dose-optimization stage, with ~50 subjects randomized 1:1 at 4.3 mg/kg Q3W or 5.2 mg/kg Q3W + prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg Q3W. Part 2 will commence with the selected optimized dose versus investigator’s choice chemotherapy, with a 2:1 randomization schedule. Key inclusion criteria: progressive PROC, up to 3 prior regimens, TPS of ≥25% for FolRα expression, and measurable disease. Key exclusion criteria: primary platinum refractory disease and prior treatment with a FolRα ADC or ADC-containing tubulin inhibitor.

Current Trial Status Currently enrolling

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