Highlights
- •Intraperitoneal Olvi-Vec was well tolerated in this phase 1 study of platinum-resistant/refractory ovarian cancer.
- •Nausea, fever, and abdominal distension were the most common treatment-related adverse events.
- •The ORR with monotherapy Olvi-Vec was 9%, stable disease ≥15 weeks was 46%, median PFS was 15.7 (95% CI: 5.7–34.5) weeks.
- •Three patients had extended overall survival (33.6 to 59+ months) following additional cytotoxic therapies.
- •Virus-induced tumor-specific T-cell activation in blood and CD8+ T-cell infiltration into tumor tissue were demonstrated.
Abstract
Objective
Our objective was to assess safety and adverse events associated with intraperitoneal
Olvi-Vec virotherapy in patients with platinum-resistant or refractory ovarian cancer
(PRROC). Secondary objectives included objective response rate (ORR) per RECIST 1.1
and progression-free survival (PFS).
Methods
Olvi-Vec is a modified vaccinia virus that causes oncolysis and immune activation.
An open-label phase 1b trial using a 3 + 3 dose escalation was conducted. Intraperitoneal
Olvi-Vec was given as monotherapy in two consecutive daily doses. Translational analyses
included anti-virus antibody levels, viral shedding, circulating tumor cells (CTCs)
and T cells.
Results
Twelve patients (median age: 69 years, range: 45–77) with median 5 prior therapies
(range: 2–10) and 2 prior platinum lines (range: 1–5) were enrolled. There were three
dose level cohorts: 3 × 109 (n = 6), 1 × 1010 (n = 5), and 2.5 × 1010 (n = 1) plaque forming units (PFU)/day on two consecutive days. Treatment-related adverse
events (TRAEs) included G1/G2 nausea (n = 6), fever (n = 6), abdominal distention (n = 5), and abdominal pain (n = 4). There were no Grade 4 TRAEs, no dose relationship to TRAEs, and no deaths attributed
to Olvi-Vec. The ORR was 9% (1/11). Stable disease (SD) was 64% (7/11), and SD ≥15 weeks
was 46% (5/11). Median PFS was 15.7 weeks (95%CI: 5.7–34.5), including extended PFS
in four patients (23.2, 34.5, 59.4+ and 70.8 weeks). Three patients had extended overall
survival (deceased 33.6 months, and alive with disease at 54 and 59 months). CTCs
diminished in 6/8 (75%) baseline-positive patients. Immune activation was demonstrated
from virus-enhanced tumor infiltration of CD8+ T-cells and activation of tumor-specific
T-cells in peripheral blood.
Conclusions
Oncolytic viral therapy with intraperitoneal Olvi-Vec showed promising safety, clinical
activities, and immune activation in patients with PRROC, warranting further clinical
investigation.
Keywords
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Article info
Publication history
Published online: October 19, 2021
Accepted:
October 10,
2021
Received in revised form:
October 1,
2021
Received:
August 25,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
