Highlights
- •Vigil (DNA engineered immunotherapy), well tolerated in frontline ovarian cancer.
- •Significant induction of delay in relapse (p = 0.033) shown between Vigil/control.
- •Correlation of T cell activation (ELISPOT response) and clinical benefit
Abstract
Objectives
The majority of women with Stage III/IV ovarian cancer who achieve clinical complete
response with frontline standard of care will relapse within 2 years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor
cell (EATC) product, demonstrated safety and induction of circulating activated T-cells
against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives
for this study include evaluation of safety, immune response and recurrence free survival
(RFS).
Methods
This is a Phase II crossover trial of Vigil (1.0 × 107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer
patients achieving cCR (normal imaging, CA-125 ≤ 35 units/ml, physical exam, and no symptoms suggestive of the presence of active disease)
following primary surgical debulking and carboplatin/paclitaxel adjuvant or neoadjuvant
chemotherapy. Patients received Vigil or standard of care during the maintenance period.
Results
Forty-two patients were entered into trial, 31 received Vigil and 11 received standard
of care. No ≥ Grade 3 toxicity related to product was observed. A marked induction of circulating
activated T-cell population was observed against individual, pre-processed autologous
tumor in the Vigil arm as compared to pre-Vigil baseline using IFNγ ELISPOT response
(30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134
spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement
was improved (mean 826 days/median 604 days in the Vigil arm from mean 481 days/median 377 days in the control arm, p = 0.033).
Conclusion
In conjunction with the demonstrated safety, the high rate of induction of T-cell
activation and correlation with improvement in RFS justify further Phase II/III assessment
of Vigil.
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Article info
Publication history
Published online: September 24, 2016
Accepted:
September 19,
2016
Received in revised form:
September 15,
2016
Received:
July 27,
2016
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
