A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, FT, or PP Cancer in 1st Remission

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A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission 

 Patient Characteristics

Twenty-four patients with advanced-stage, poor-risk ovarian carcinoma were enrolled on clinical trial NCT01248273 between 01/2011 and 09/2013. Patient characteristics are shown in Table 1. Patients had a median age of 54 years (range, 36–68 years). Primary sites included the ovary, 20; fallopian tube, three; and peritoneum, one. KPS ranged from 80–100%. The majority of patients were Caucasian (n = 22, 92%), and two patients were Asian (8%). Eighteen patients (75%) had stage III disease, and the remaining 6 (25%) had stage IV disease at diagnosis. Twenty-two patients (92%) had high-grade serous histology and two patients (8%) had clear cell histology.

 

3.4. Progression-Free Survival

Although clinical outcome was not the study end point of this phase I study, the PFS is illustrated in Figure 3. PFS was calculated for 20 events and censored at 24.6, 27, 42 and 46.5 months for four patients who continued in remission at last follow-up. The small patient numbers preclude any correlation of antibody response generated with PFS. It was observed that one of the patients with the longest PFS generated a response to all five antigens. At last follow-up, six patients had died of disease and the remaining 18 were alive. For this high-risk group, the median PFS was 12.6 months (95% CI, 10.2–29.5 months) from start of adjuvant chemotherapy.

  
5. Conclusions

The unimolecular vaccine was shown to be safe and immunogenic. Nine (75%) of 12 patients treated at the highest dose of 100 mcg and 20 (83%) of all 24 patients treated on the study responded to at least three antigens. 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 [13]. This unimolecular construct greatly simplifies manufacturing, permits the addition or exchange of multiple new antigens, and allows for easy scalability.