890P - Unimolecular pentavalent (Globo-H-GM2-sTn-TF-Tn) immunization of patients (pts) with epithelial ovarian(EOC), fallopian tube, or peritoneal cancer...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Ovarian Cancer
Cancer Immunology and Immunotherapy
Presenter Roisin O'Cearbhaill
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors R.E. O'Cearbhaill1, A. Iasonos2, G. Ragupathi3, S. Danishefsky3, P. Sabbatini1
  • 1Gynecologic Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Epidemiology-biostatistics, MSKCC, 10065 - New York/US
  • 3Clinical Immunology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US

Abstract

Aim

We conducted an IRB-approved phase I study to evaluate the safety and immunogenicity of a unimolecular pentavalent carbohydrate vaccine, bearing five antigens (AGs), Globo-H, GM2, STn, TF and Tn conjugated to keyhole limpet hemocyanin(KLH) and mixed with QS-21 adjuvant, in EOC pts in 1st remission. We previously demonstrated the safe induction of antibody (ab) responses to these individual AGs in a series of monovalent-KLH trials.

Methods

Pts with stage III or IV OC in 1st remission were enrolled from 1/2011-09/2013. Three dose levels were planned (25, 50,100mcg) with 3 cohorts of 6 pts to be treated at each dose level (with an additional expansion cohort of 6 pts at the MTD). The schedule was 5 vaccines administered subcutaneously during weeks 1, 2, 3, 7 and 19. Serologic IgM and IgG responses were measured by ELISA against each AG. Serologic response per AG was defined as 1) Ab titer ≥1:80 for pts with no detectable baseline titer or 2) Ab titer ≥8-fold increase over baseline if detectable baseline titer. If ≥4 of 12 pts treated at the MTD were immune responders for ≥3AGs then the study would be considered positive.

Results

n = 24 Median age 56yrs (36-79); 22 (92%) high grade serous; 21 (88%) stage III; 3 (12%) stage IV. No DLTs. Immune Results: IgG +/or IgM: ≥3 AGs 20/24 pts (83%). At MTD 100mcg n = 12: IgG +/or IgM: ≥3 AGs 9/12 pts (75%), ≥4 AGs 7/12 pts (58%), 5 AGs 3/12 pts (25%). IgM: ≥1 AG in pts, ≥3 AGs in pts. IgG: ≥1 AG in pts, ≥3 AGs in pts. With a median follow-up of 19mos (2-39), 8pts (33%) had recurred and 4 pts (17%) had died.

Immune Response
AG GM2 GM2 GloboH GloboH Tn Tn TF TF sTn sTn
Ab IgM IgG IgM IgG IgM IgG IgM IgG IgM IgG
n = 12 MTD responders 3 2 1 7 7 10 8 3 11 8

Conclusions

The unimolecular vaccine was shown to be safe and immunogenic. 9/12 (75%) pts at MTD (83% of all treated pts) responded to ≥3 AGs. This immune response was comparable to our previously reported immune response in a phase I trial of a heptavalent vaccine with individual antigens conjugated to KLH. The unimolecular construct warrants further investigation and permits multiple AG-targeting. The construct greatly simplifies manufacturing and allows easy scalability of the vaccine.

Disclosure

S. Danishefsky: Dr Danifshesky has financial interest in the vaccine being studied. MSKCC holds the patent on this invention.

All other authors have declared no conflicts of interest.