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372 Safety and activity of the anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer
  1. A Santin1,
  2. I Vergote2,
  3. A Martín3,
  4. K Moore4,
  5. A Oaknin5,
  6. I Romero6,
  7. S Diab7,
  8. LJ Copeland8,
  9. B Monk9,
  10. R Coleman10,
  11. TJ Herzog11,
  12. J Siegel12,
  13. A Walter13,
  14. BH Childs12,
  15. C Elbi12 and
  16. I Bulat14
  1. 1Yale School of Medicine, USA
  2. 2University Hospitals Leuven, Leuven Cancer Institute, Belgium
  3. 3Clinica Universidad de Navarra, Spain
  4. 4University of Oklahoma Health Sciences Center, USA
  5. 5Vall d’Hebron Institute of Oncology, Spain
  6. 6Instituto Valenciano De Oncologia, Spain
  7. 7Rocky Mountain Cancer Centers, USA
  8. 8Ohio State University Medical Center, USA
  9. 9Arizona Oncology, USA
  10. 10McKesson Corporation, USA
  11. 11University of Cincinnati Cancer Institute, USA
  12. 12Bayer HealthCare Pharmaceuticals, Inc., USA
  13. 13Bayer AG, Germany
  14. 14ARENSIA Exploratory Medicine, Institute of Oncology Unit, Moldova


Introduction Treatment options for platinum-resistant ovarian cancer (PROC) remain a high medical need. Mesothelin is highly expressed in PROC. Anetumab ravtansine (ARv) is an antibody–drug conjugate that selectively targets mesothelin, consisting of a fully human anti-mesothelin monoclonal antibody conjugated to the cytotoxic maytansinoid tubulin inhibitor DM4.

Methods This phase Ib, open-label, dose-escalation (modified 3+3 design, n=9) and expansion study (n=56) evaluated the safety/tolerability and clinical activity of ARv and pegylated liposomal doxorubicin (PLD, 30 mg/m² Q3W) in PROC. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST v1.1), and progression-free survival (PFS) were determined. Biomarker samples were assessed by ELISA, next-generation sequencing, and expression profiling.

Results ARv/PLD combination was safe and tolerated. No DLT was observed. MTD of ARv was 6.5 mg/kg Q3W. The most common ARv-related adverse events were nausea (38.5%), decreased appetite (30.8%), corneal disorder (29.2%), fatigue (29.2%), diarrhea (24.6%), and AST increase (21.5%).

In all measurable or evaluable patients (n=65), objective response rate (ORR) was 28% (95% CI 16.0–38.5%), including one complete and 17 partial responses with a median PFS of 5.1 months. In an exploratory subset of patients (n=19) who received ≤3 prior lines of therapy with high mesothelin expression, the ORR was 42% with a median duration of response of 36 weeks. Median PFS was 8.5 months.

Conclusions/Implications These results established the RP2D, schedule, and mesothelin-positive target population of the ARv/PLD combination for the phase III study in PROC. Molecular profiling and correlation with observed clinical activity will be presented.

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