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> Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: A phase 1 clinical trial
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Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: A phase 1 clinical trial
Moreno, V.
;
Barretina-Ginesta, M.-P.
;
García-Donas, J.
;
Jayson, G.C.
;
Roxburgh, P.
;
Márquez Vázquez, R.
;
Michael, A.
;
Antón-Torres, A.
(Universidad de Zaragoza)
;
Brown, R.
;
Krige, D.
;
Champion, B.
;
McNeish, I.
Resumen:
Background 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.
Idioma:
Inglés
DOI:
10.1136/jitc-2021-003645
Año:
2021
Publicado en:
Journal for immunotherapy of cancer
9, 12 (2021), e003645 [14 pp.]
ISSN:
2051-1426
Factor impacto JCR:
12.485 (2021)
Categ. JCR:
ONCOLOGY
rank: 25 / 245 = 0.102
(2021)
- Q1
- T1
Categ. JCR:
IMMUNOLOGY
rank: 18 / 163 = 0.11
(2021)
- Q1
- T1
Factor impacto CITESCORE:
14.3 -
Biochemistry, Genetics and Molecular Biology
(Q1) -
Immunology and Microbiology
(Q1) -
Pharmacology, Toxicology and Pharmaceutics
(Q1) -
Medicine
(Q1)
Factor impacto SCIMAGO:
3.45 -
Cancer Research
(Q1) -
Immunology
(Q1) -
Pharmacology
(Q1) -
Oncology
(Q1) -
Molecular Medicine
(Q1)
Tipo y forma:
Article (Published version)
Área (Departamento):
Area Medicina
(
Dpto. Medicina, Psiqu. y Derm.
)
Exportado de SIDERAL (2023-05-18-14:20:44)
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Notice créée le 2022-05-27, modifiée le 2023-05-19
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