Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial.

Autor:	Rocconi RP; Division of Gynecologic Oncology, University of South Alabama-Mitchell Cancer Institute, Mobile, AL, USA., Grosen EA; Department of Obstetrics and Gynecology, Cancer Care Northwest, Spokane, WA, USA., Ghamande SA; Section of Gynecologic Oncology, Augusta University, Augusta, GA, USA., Chan JK; Division of Gynecologic Oncology, California Pacific/Palo Alto Medical Foundation, Sutter Center Research Institute, San Francisco, CA, USA., Barve MA; Department of Oncology, Mary Crowley Cancer Research Centers, Dallas, TX, USA; Department of Oncology, Texas Oncology, Dallas, TX, USA., Oh J; Department of Oncology, Texas Oncology, Dallas, TX, USA., Tewari D; Department of Obstetrics and Gynecology, Kaiser Permanente, Irvine, CA, USA., Morris PC; Division of Gynecologic Oncology, Nebraska Methodist Hospital, Omaha, NE, USA., Stevens EE; Department of Gynecologic Oncology, Billings Clinic, Billings, MT, USA., Bottsford-Miller JN; Department of Gynecologic Oncology, Billings Clinic, Billings, MT, USA., Tang M; Stats Department, StatBeyond Consulting, Irvine, CA, USA., Aaron P; Department of Medical Affairs, Gradalis, Carollton, TX, USA., Stanbery L; Department of Medical Affairs, Gradalis, Carollton, TX, USA., Horvath S; Department of Site Research, Gradalis, Carollton, TX, USA., Wallraven G; Department of Clinical and Regulatory Operations, Gradalis, Carollton, TX, USA., Bognar E; Department of CMC Operations, Gradalis, Carollton, TX, USA; Department of CMC Operations, Gradalis, Carollton, TX, USA; Department of CMC Operations, Gradalis, Carollton, TX, USA., Manning L; Department of Medical Affairs, Gradalis, Carollton, TX, USA., Nemunaitis J; Department of Medical Affairs, Gradalis, Carollton, TX, USA. Electronic address: jnemunaitis@gradalisinc.com., Shanahan D; Management Department, Gradalis, Carollton, TX, USA; Management Department, Gradalis, Carollton, TX, USA; Management Department, Gradalis, Carollton, TX, USA., Slomovitz BM; Department of Obstetrics and Gynecology, Broward Health, Fort Lauderdale, FL, USA; Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA., Herzog TJ; Department of Obstetrics and Gynecology, University of Cincinnati Cancer Center, Cincinnati, OH, USA., Monk BJ; Department of Obstetrics and Gynecology, Arizona Oncology, Phoenix, AZ, USA., Coleman RL; US Oncology Research, The Woodlands, TX, USA.
Jazyk:	angličtina
Zdroj:	The Lancet. Oncology [Lancet Oncol] 2020 Dec; Vol. 21 (12), pp. 1661-1672.
DOI:	10.1016/S1470-2045(20)30533-7
Abstrakt:	Background: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-β1 and TGF-β2. The aim of this study was to determine the safety and efficacy of gemogenovatucel-T in front-line ovarian cancer maintenance. Methods: This randomised, double-blind, placebo-controlled, phase 2b trial involved 25 hospitals in the USA. Women aged 18 years and older with stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer in clinical complete response after a combination of surgery and five to eight cycles of chemotherapy involving carboplatin and paclitaxel, and an Eastern Cooperative Oncology Group status of 0 or 1 were eligible for inclusion in the study. Patients were randomly assigned (1:1) to gemogenovatucel-T or placebo by an independent third party interactive response system after successful screening using randomly permuted block sizes of two and four and stratified by extent of surgical cytoreduction and neoadjuvant versus adjuvant chemotherapy. Gemogenovatucel-T (1 × 10 7 cells per injection) or placebo was administered intradermally (one per month) for a minimum of four and up to 12 doses. Patients, investigators, and clinical staff were masked to patient allocation until after statistical analysis. The primary endpoint was recurrence-free survival, analysed in the per-protocol population. All patients who received at least one dose of gemogenovatucel-T were included in the safety analysis. The study is registered with ClinicalTrials.gov, NCT02346747. Findings: Between Feb 11, 2015, and March 2, 2017, 310 patients consented to the study at 22 sites. 217 were excluded. 91 patients received gemogenovatucel-T (n=47) or placebo (n=44) and were analysed for safety and efficacy. The median follow-up from first dose of gemogenovatucel-T was 40·0 months (IQR 35·0-44·8) and from first dose of placebo was 39·8 months (35·5-44·6). Recurrence-free survival was 11·5 months (95% CI 7·5-not reached) for patients assigned to gemogenovatucel-T versus 8·4 months (7·9-15·5) for patients assigned to placebo (HR 0·69, 90% CI 0·44-1·07; one-sided p=0·078). Gemogenovatucel-T resulted in no grade 3 or 4 toxic effects. Two patients in the placebo group had five grade 3 toxic events, including arthralgia, bone pain, generalised muscle weakness, syncope, and dyspnea. Seven patients (four in the placebo group and three in the gemogenovatucel-T group) had 11 serious adverse events. No treatment-related deaths were reported in either of the groups. Interpretation: Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated but the primary endpoint was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted. Funding: Gradalis. (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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