Factors associated with extended survival for patients with platinum-resistant ovarian cancer treated with modified vaccinia oncolytic virotherapy.

Abstract

e17070 Background: VIRO-15 phase IB trial included 11 patients (pts) with platinum-resistant ovarian cancer (PROC), extensive tumor burden and a median of 5 prior lines of therapy who were given intra-peritoneal Olvi-Vec (GL-ONC1), a modified vaccinia oncolytic virus (OV). Four pts had apparent clinical benefit with > 5 mos progression-free survival (PFS) following OV. This analysis aimed to determine factors that predict clinical benefit from OV. Methods: Comparative analyses included: anti-vaccinia neutralizing antibody (NA) as a measure of immune-competence, virus-encoded glucuronidase activity (GA) indicating viral replication, tumor shrinkage by RECIST 1.1, tumor burden (serum LDH), PD-L1 status, Prognostic Nutritional Index (PNI), absolute lymphocyte count, C-reactive protein, albumin, ECOG performance score (PS), no. of prior lines of therapy and platinum therapies, BRCA status, CA125 tumor marker, & circulating tumor cells (CTCs). Results: Mean age was 66.3±9.3 years and BMI 24.8±4.7 kg/m2. Median prior chemotherapy lines = 5 (range 2-10), median prior platinum lines = 3 (range 2-6), and 9 pts had prior Avastin. Following OV, 4 pts (Group A) had mean PFS 10.9±5.1 (range 5.4-16.4) mos compared to 7 pts (Group B), with mean PFS 2.4±1.1 (range 1.3-4.1) mos ( p< 0.05). Mean OS for Group A was 21.7±8.2 (range 7.8-28.3) mos vs 3.6±1.5 (range 1.6-6.2) mos for Group B ( p< 0.05). 3 Group A pts are alive with PS 0, and one with stable disease died at 8 mos from pulmonary embolism. Factors that predicted clinical benefit were: i) PNI [mean 49.0±5.7 vs 42.1±4.3 ( p< 0.05)], ii) Week-5 CA125 values < Week-2 [4/4 vs 0/7 (p < 0.01)], iii) absence of CTC [3/4 vs 1/7 pts ( p< 0.05)]. Baseline PD-L1 expression and BRCA status were not predictive markers. Conclusions: Factors associated with clinical benefit using GL-ONC1 monotherapy in PROC include PNI > 44.5, absence of CTCs, and Week-5 CA125 less than Week-2 levels. Absent these factors, cytotoxic therapy should be considered by Week-6 following GL-ONC1. Three patients are currently alive at 22.8-28.2 mos, following additional therapies. A multi-institutional phase II trial is currently enrolling. Clinical trial information: NCT02759588.