A phase 1b study of intraperitoneal oncolytic viral immunotherapy in platinum-resistant or refractory ovarian cancer.

Abstract

OBJECTIVE\nOur 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).\n\n\nMETHODS\nOlvi-Vec is a modified vaccinia virus that causes oncolysis and immune activation. An open-label phase 1b trial using a 3\xa0+\xa03 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.\n\n\nRESULTS\nTwelve patients (median age: 69\xa0years, 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\xa0×\xa0109 (n\xa0=\xa06), 1\xa0×\xa01010 (n\xa0=\xa05), and 2.5\xa0×\xa01010 (n\xa0=\xa01) plaque forming units (PFU)/day on two consecutive days. Treatment-related adverse events (TRAEs) included G1/G2 nausea (n\xa0=\xa06), fever (n\xa0=\xa06), abdominal distention (n\xa0=\xa05), and abdominal pain (n\xa0=\xa04). 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\xa0weeks was 46% (5/11). Median PFS was 15.7\xa0weeks (95%CI: 5.7-34.5), including extended PFS in four patients (23.2, 34.5, 59.4+ and 70.8\xa0weeks). Three patients had extended overall survival (deceased 33.6\xa0months, and alive with disease at 54 and 59\xa0months). 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.\n\n\nCONCLUSIONS\nOncolytic viral therapy with intraperitoneal Olvi-Vec showed promising safety, clinical activities, and immune activation in patients with PRROC, warranting further clinical investigation.