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Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission
  1. Oren Smaletz1,
  2. Gustavo Ismael2,
  3. Maria Del Pilar Estevez-Diz3,
  4. Ivana L O Nascimento4,
  5. Ana Luiza Gomes de Morais5,
  6. Geraldo Felício Cunha-Junior6,
  7. Sergio J Azevedo7,
  8. Venancio A Alves8,
  9. Ana Maria Moro9,
  10. Fernanda P Yeda9,
  11. Mariana Lopes dos Santos9,
  12. Indrani Majumder10 and
  13. Eric W Hoffman11
  1. 1 Oncology Department, Hospital Israelita Albert Einstein, Sao Paulo, Sao Paulo, Brazil
  2. 2 Amaral Carvalho Hospital, Jau, Sao Paulo, Brazil
  3. 3 Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
  4. 4 Núcleo de Oncologia da Bahia, Salvador, Bahia, Brazil
  5. 5 Hospital Erasto Gaertner, Curitiba, Paraná, Brazil
  6. 6 Cetus Hospital-Dia Oncologia e Hospital da Baleia, Belo Horizonte, Brazil
  7. 7 Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
  8. 8 Pathology Department, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
  9. 9 Butantan Institute, Sao Paulo, Sao Paulo, Brazil
  10. 10 Recepta Biopharma, Sao Paulo, Sao Paulo, Brazil
  11. 11 Ludwig Institute for Cancer Research Ltd, New York, New York, USA
  1. Correspondence to Dr Oren Smaletz, Oncology Department, Hospital Israelita Albert Einstein, Sao Paulo 05651-901, Brazil; oren.smaletz{at}einstein.br

Abstract

Objective To investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.

Methods This single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.

Results Twenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).

Conclusions Hu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.

Trial registration NCT01137071.

  • ovarian cancer

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Footnotes

  • Contributors OS: conceptualization, methodology, investigation, resources, writing original draft, supervision. GI: investigation, resources, writing, review, editing. MDPE-D: investigation, resources, writing, review, editing. ILON: investigation, resources, writing, review, editing. ALGdM: investigation, resources, writing, review, editing. GFC-J: investigation, resources, writing, review, editing. SJA: investigation, resources, writing, review, editing. VAA: investigation, resources, writing, review, editing. AMM: investigation, resources, writing, review, editing. FPY: investigation, resources, writing, review, editing. MLdS: investigation, resources, writing original draft. IM: project administration, data curation, formal analysis, funding acquisition, writing, review, editing. EWH: conceptualization, writing, review, editing.

  • Funding This study was funded by Recepta Biopharma, São Paulo, Brazil.

  • Competing interests Dr. Smaletz reports non-financial support from Recepta Biopharma, during the conduct of the study; personal fees from Astra Zeneca, outside the submitted work. Dr. Ismael has nothing to disclose. Dr. Estevez-Diz has nothing to disclose. Dr. Nascimento has nothing to disclose. Dr. Gomes de Morais has nothing to disclose. Dr. Azevedo has nothing to disclose. Dr. Alves received a grant from Recepta Biopharma, including personal fees regarding his activities in this study. Dr. Moro reports grants from FINEP, personal fees from Fundação Butantan, during the conduct of the study. Dr. Yeda reports personal fees from Recepta Biopharma, personal fees from Fundação Butantan, during the conduct of the study. Dr. Lopes dos Santos has nothing to disclose. Dr. Majumder reports grants from FINEP, during the conduct of the study. Dr. Hoffman has nothing to disclose.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. In accordance with the journal’s guidelines, we will provide our data for the reproducibility of this study in other centers if such is requested.

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