Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study

  • Ann Oncol. 2018 Apr 1;29(4):917-923. doi: 10.1093/annonc/mdy023.
S Banerjee  1 ,  A M Oza  2 ,  M J Birrer  3 ,  E P Hamilton  4 ,  J Hasan  5 ,  A Leary  6 ,  K N Moore  7 ,  B Mackowiak-Matejczyk  8 ,  J Pikiel  9 ,  I Ray-Coquard  10 ,  P Trask  11 ,  K Lin  11 ,  E Schuth  11 ,  A Vaze  11 ,  Y Choi  11 ,  J C Marsters  11 ,  D J Maslyar  11 ,  V Lemahieu  11 ,  Y Wang  11 ,  E W Humke  11 ,  J F Liu  12
Affiliations
  • 1. Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK.
  • 2. Princess Margaret Hospital, Toronto, Canada.
  • 3. Massachusetts General Hospital, Boston, USA; Harvard Medical School, Boston, USA.
  • 4. Sarah Cannon Research Institute, Nashville, USA; Tennessee Oncology, Nashville, USA.
  • 5. The Christie Hospital, Manchester, UK.
  • 6. Gustave Roussy Cancer Centre, Paris, France.
  • 7. University of Oklahoma Health Sciences Center, Oklahoma City, USA.
  • 8. Bialystok Oncology Center, Bialystok, Poland.
  • 9. Regional Center of Oncology, Gdańsk, Poland.
  • 10. Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes, Lyon, France.
  • 11. Genentech, Inc., South San Francisco, USA.
  • 12. Harvard Medical School, Boston, USA; Gynecologic Oncology Program, Dana-Farber Cancer Institute, Boston, USA. Electronic address: [email protected].
PMID: 29401246 DOI: 10.1093/annonc/mdy023
Abstract

Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl Auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian Cancer (OC) patients.

Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients.

Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy.

Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl Auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC.

Clinical trials.gov: NCT01991210.

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