000112478 001__ 112478
000112478 005__ 20230519145434.0
000112478 0247_ $$2doi$$a10.1136/jitc-2021-003645
000112478 0248_ $$2sideral$$a127520
000112478 037__ $$aART-2021-127520
000112478 041__ $$aeng
000112478 100__ $$aMoreno, V.
000112478 245__ $$aSafety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: A phase 1 clinical trial
000112478 260__ $$c2021
000112478 5060_ $$aAccess copy available to the general public$$fUnrestricted
000112478 5203_ $$aBackground Treatment outcomes remain poor in recurrent platinum-resistant ovarian cancer. Enadenotucirev, a tumor-selective and blood stable adenoviral vector, has demonstrated a manageable safety profile in phase 1 studies in epithelial solid tumors. Methods We conducted a multicenter, open-label, phase 1 dose-escalation and dose-expansion study (OCTAVE) to assess enadenotucirev plus paclitaxel in patients with platinum-resistant epithelial ovarian cancer. During phase 1a, the maximum tolerated dose of intraperitoneally administered enadenotucirev monotherapy (three doses; days 1, 8 and 15) was assessed using a 3+3 dose-escalation model. Phase 1b included a dose-escalation and an intravenous dosing dose-expansion phase assessing enadenotucirev plus paclitaxel. For phase 1a/b, the primary objective was to determine the maximum tolerated dose of enadenotucirev (with paclitaxel in phase 1b). In the dose-expansion phase, the primary endpoint was progression-free survival (PFS). Additional endpoints included response rate and T-cell infiltration. Results Overall, 38 heavily pretreated patients were enrolled and treated. No dose-limiting toxicities were observed at any doses. However, frequent catheter complications led to the discontinuation of intraperitoneal dosing during phase 1b. Intravenous enadenotucirev (1×10 12 viral particles; days 1, 3 and 5 every 28-days for two cycles) plus paclitaxel (80 mg/m 2; days 9, 16 and 23 of each cycle) was thus selected for dose-expansion. Overall, 24/38 (63%) patients experienced at least 1 Grade =3 treatment-emergent adverse event (TEAE); most frequently neutropenia (21%). Six patients discontinued treatment due to TEAEs, including one patient due to a grade 2 treatment-emergent serious AE of catheter site infection (intraperitoneal enadenotucirev monotherapy). Among the 20 patients who received intravenous enadenotucirev plus paclitaxel, 4-month PFS rate was 64% (median 6.2 months), objective response rate was 10%, 35% of patients achieved stable disease and 65% of patients had a reduction in target lesion burden at =1 time point. Five out of six patients with matched pre-Treatment and post-Treatment biopsies treated with intravenous enadenotucirev plus paclitaxel had increased (mean 3.1-fold) infiltration of CD8 +T cells in post-Treatment biopsies. Conclusions Intravenously dosed enadenotucirev plus paclitaxel demonstrated manageable tolerability, an encouraging median PFS and increased tumor immune-cell infiltration in platinum-resistant ovarian cancer. Trial registration number NCT02028117. © 2021 BMJ Publishing Group. All rights reserved.
000112478 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000112478 590__ $$a12.485$$b2021
000112478 592__ $$a3.45$$b2021
000112478 594__ $$a14.3$$b2021
000112478 591__ $$aONCOLOGY$$b25 / 245 = 0.102$$c2021$$dQ1$$eT1
000112478 593__ $$aCancer Research$$c2021$$dQ1
000112478 591__ $$aIMMUNOLOGY$$b18 / 163 = 0.11$$c2021$$dQ1$$eT1
000112478 593__ $$aImmunology$$c2021$$dQ1
000112478 593__ $$aPharmacology$$c2021$$dQ1
000112478 593__ $$aOncology$$c2021$$dQ1
000112478 593__ $$aMolecular Medicine$$c2021$$dQ1
000112478 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000112478 700__ $$aBarretina-Ginesta, M.-P.
000112478 700__ $$aGarcía-Donas, J.
000112478 700__ $$aJayson, G.C.
000112478 700__ $$aRoxburgh, P.
000112478 700__ $$aMárquez Vázquez, R.
000112478 700__ $$aMichael, A.
000112478 700__ $$0(orcid)0000-0002-9159-4988$$aAntón-Torres, A.$$uUniversidad de Zaragoza
000112478 700__ $$aBrown, R.
000112478 700__ $$aKrige, D.
000112478 700__ $$aChampion, B.
000112478 700__ $$aMcNeish, I.
000112478 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000112478 773__ $$g9, 12 (2021), e003645 [14 pp.]$$pJ. immunotherap. cancer$$tJournal for immunotherapy of cancer$$x2051-1426
000112478 8564_ $$s2078540$$uhttps://zaguan.unizar.es/record/112478/files/texto_completo.pdf$$yVersión publicada
000112478 8564_ $$s3249126$$uhttps://zaguan.unizar.es/record/112478/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000112478 909CO $$ooai:zaguan.unizar.es:112478$$particulos$$pdriver
000112478 951__ $$a2023-05-18-14:20:44
000112478 980__ $$aARTICLE