Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer.
OBJECTIVE
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 (1.0×107cells/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 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).


CONCLUSIONS
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.
Texas Oncology, P.A., Dallas, TX, United States.
Jonathan
J
Oh
Mary Crowley Cancer Research Centers, Dallas, TX, United States; Texas Oncology, P.A., Dallas, TX, United States.
Minal
M
Barve
Texas Oncology, P.A., Dallas, TX, United States.
Carolyn M
CM
Matthews
Texas Oncology, P.A., Dallas, TX, United States.
E Colin
EC
Koon
North Texas Gynecologic Oncology, Dallas, TX, United States.
Thomas P
TP
Heffernan
Texas Oncology, P.A., Dallas, TX, United States.
Bruce
B
Fine
Cancer Care Northwest, Spokane, WA, United States.
Elizabeth
E
Grosen
Cancer Care Northwest, Spokane, WA, United States.
Melanie K
MK
Bergman
Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
Evelyn L
EL
Fleming
Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
Leslie R
LR
DeMars
Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
Loyd
L
West
Florida Cancer Specialists, West Palm Beach, FL, United States.
Daniel L
DL
Spitz
Florida Cancer Specialists, West Palm Beach, FL, United States.
Howard
H
Goodman
Texas Oncology, Fort Worth, TX, United States.
Kenneth C
KC
Hancock
Gradalis, Inc., Dallas, TX, United States.
Gladice
G
Wallraven
Gradalis, Inc., Dallas, TX, United States.
Padmasini
P
Kumar
Gradalis, Inc., Dallas, TX, United States.
Ernest
E
Bognar
Gradalis, Inc., Dallas, TX, United States.
Luisa
L
Manning
Gradalis, Inc., Dallas, TX, United States.
Beena O
BO
Pappen
Mary Crowley Cancer Research Centers, Dallas, TX, United States.
Ned
N
Adams
Mary Crowley Cancer Research Centers, Dallas, TX, United States; Gradalis, Inc., Dallas, TX, United States.
Neil
N
Senzer
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.
John
J
Nemunaitis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018269:Carcinoma, Endometrioid / Q000188:drug therapy* / Q000473:pathology; D018592:Cross-Over Studies; D065426:Cytoreduction Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D013601:T-Lymphocytes
D019496:Cancer Vaccines; C573235:FANG vaccine; D016190:Carboplatin; D017239:Paclitaxel