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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.
)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
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