Jonathan Oh1, Minal Barve2, Carolyn M Matthews1, E Colin Koon1, Thomas P Heffernan3, Bruce Fine1, Elizabeth Grosen4, Melanie K Bergman4, Evelyn L Fleming5, Leslie R DeMars5, Loyd West5, Daniel L Spitz6, Howard Goodman6, Kenneth C Hancock7, Gladice Wallraven8, Padmasini Kumar8, Ernest Bognar8, Luisa Manning8, Beena O Pappen8, Ned Adams9, Neil Senzer10, John Nemunaitis11. 1. Texas Oncology, P.A., Dallas, TX, United States. 2. Mary Crowley Cancer Research Centers, Dallas, TX, United States; Texas Oncology, P.A., Dallas, TX, United States. 3. North Texas Gynecologic Oncology, Dallas, TX, United States. 4. Cancer Care Northwest, Spokane, WA, United States. 5. Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States. 6. Florida Cancer Specialists, West Palm Beach, FL, United States. 7. Texas Oncology, Fort Worth, TX, United States. 8. Gradalis, Inc., Dallas, TX, United States. 9. Mary Crowley Cancer Research Centers, Dallas, TX, United States. 10. Mary Crowley Cancer Research Centers, Dallas, TX, United States; Gradalis, Inc., Dallas, TX, United States. 11. Mary Crowley Cancer Research Centers, Dallas, TX, United States; Texas Oncology, P.A., Dallas, TX, United States; Gradalis, Inc., Dallas, TX, United States; Medical City Dallas Hospital, Dallas, TX, United States. Electronic address: jnemunaitis@marycrowley.org.
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 2years. 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≤35units/ml, physical exam, and no symptoms suggestive of the presence of active disease) following primary surgical debulking andcarboplatin/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 826days/median 604days in the Vigil arm from mean 481days/median 377days 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.
RCT Entities:
OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. 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 cancerpatients achieving cCR (normal imaging, CA-125≤35units/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 826days/median 604days in the Vigil arm from mean 481days/median 377days 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.
Authors: Matthew J Lin; Judit Svensson-Arvelund; Gabrielle S Lubitz; Aurélien Marabelle; Ignacio Melero; Brian D Brown; Joshua D Brody Journal: Nat Cancer Date: 2022-08-23
Authors: Sterre T Paijens; Ninke Leffers; Toos Daemen; Wijnand Helfrich; H Marike Boezen; Ben J Cohlen; Cornelis Jm Melief; Marco de Bruyn; Hans W Nijman Journal: Cochrane Database Syst Rev Date: 2018-09-10
Authors: Elyssa Sliheet; Molly Robinson; Susan Morand; Khalil Choucair; David Willoughby; Laura Stanbery; Phylicia Aaron; Ernest Bognar; John Nemunaitis Journal: Cancer Gene Ther Date: 2021-11-16 Impact factor: 5.854