Small Phase I Study Reports 2 to 4 Year Ovarian Cancer Remission in 30% of Women Who Received a NY-ESO-1 Vaccine

Three of nine patients (33%) remain in complete clinical remission at 25, 38, and 52 months, respectively.

The cancer-testis antigen NY-ESO-1 is expressed in greater than 40% of advanced epithelial ovarian cancers and represents a promising immunotherapeutic target. In a small Phase I (safety and immunogenicity) clinical trial conducted by Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, nine “high-risk” epithelial ovarian cancer patients, who were in first clinical remission after primary surgery and chemotherapy, received NY-ESO-1b peptide and Montanide ISA-51 every 3 weeks in the form of five vaccinations. The “high risk” ovarian cancer patient criterion was defined as a patient who (i) received suboptimal primary debulking (remaining tumor masses with diameter of 1.0 cm or greater), or (ii) experienced a failure to normalize the CA 125 blood tumor marker by the end of the third cycle of first-line chemotherapy. In addition, each patient enrolled in the trial was required to test positive for (i) human leukocyte antigen 2A (HLA-2A) in the blood, and (ii) NY-ESO-1 or LAGE-1 tumor expression. NY-ESO-1 tumor expression was evaluated for each patient by immunohistochemistry (IHC). LAGE-1 tumor expression was evaluated for each patient by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis. For each patient, NY-ESO-1 specific humoral immunity (ELISA), T-cell immunity (tetramer and ELISPOT), and delayed-type hypersensitivity were assessed pre-vaccination and at week #1, week #4, week #7, week #10, week #13, and week #16 of the vaccination period.

The nine patients experienced treatment-related adverse events including: grade 1 fatigue, anemia, pruritus, myalgias, and hyperthyroidism; and grade 2 hypothyroidism. There were no grade 3/grade 4 adverse events. The results of the Phase I trial are set forth below.

  • Three of four patients (75%) with NY-ESO-1-positive tumor showed T-cell immunity.
  • Four of five patients (80%) with NY-ESO-1-negative tumor showed T-cell immunity.
  • At median follow-up of 11.3 months, six of nine patients (67%) have recurred, with a median progression-free survival (PFS) of 13 months.
  • Three of nine patients (33%) remain in complete clinical remission at 25, 38, and 52 months, respectively.

At the end of the Phase I trial, the trial investigators concluded that vaccination of high-risk, HLA-A2-positive epithelial ovarian cancer patients with NY-ESO-1b and Montanide has minimal toxicity and induces specific T-cell immunity in patients with both NY-ESO-1-positive and NY-ESO-1-negative tumors. Also, the trial investigators noted that additional study is necessary. For a copy of the clinical trial protocol associated with this trial, click here.

[Source: “Safety and Immunogenicity Study of NY-ESO-1b Peptide and Montanide ISA-51 Vaccination of Patients with Epithelial Ovarian Cancer in High-Risk First Remission;” Diefenbach, C.S. et. al.; Clin Cancer Res. 2008 May 1;14(9):2740-2748.]

Comment: Prior cancer vaccines targeting NY-ESO-1 overexpression in ovarian cancer tumors produced moderate success in terms of an increase in PFS. This study is particularly provocative because patients who tested positive and negative for NY-ESO-1 tumor expression experienced T-cell immunity, and “high risk” patients (including suboptimally debulked patients) experienced PFS benefit.

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