Oncolytic viruses are promising cancer immunotherapies but questions have been raised regarding their safety. Pelareorep (REOLYSIN, R), an unmodified Reovirus Dearing strain, selectively replicates and lyses cancer cells and induces anti-tumor immunity. To date, 900+ patients (pts) have been treated with intravenous (IV) pelareorep. In a phase 2 trial, its combination with paclitaxel improved overall survival (17.4m) vs paclitaxel (10.4m) in metastatic breast cancer (MBC) pts (HR 0.65, 80% CI 0.46-0.91, p = 0.1; Berstein et.al. AACR2017). A pooled analysis was thus conducted to better characterize pelareorep’s safety profile in combinations with paclitaxel.
1417 pts have been enrolled in 36 trials: 934 pts received IV pelareorep and 359 were in control arms. Data from 8 trials with paclitaxel (P), paclitaxel + pelareorep (PR), carboplatin + paclitaxel (CP) or carboplatin + paclitaxel + pelareorep (CPR) were pooled. Standard doses of P (weekly) and CP were administered. Pelareorep IV dose was 3x1010 TCID50 (5-6 doses q21-28 d). Various advanced solid tumors were evaluated, including the 81 pts with MBC.
A total of 563 pts were included in P (86), PR (95), CP (118) or CPR (264) groups. Median age (59-62 y) and ECOG 0-1 status (90-96%) were similar across the groups. All pts in P or PR had received prior chemo but only 26% in CP and 38% in CPR. Fatigue was the most common grade ≥3 treatment related adverse event (TRAE) in PR (9.5%) and CPR (8.3%) vs P (8.1%) and CP (2.5%). Grade ≥3 neutrophil count decreased and/or WBC decreased were more frequent in PR (15.8%/17.9%) than in P (5.8%/3.5%), but addition of pelareorep did not increase the frequency or severity of other grade ≥3 TRAEs with P or CP. Serious TRAEs (%) of interest in P vs PR and CP vs. CPR, included: fever (0 vs 3.2 & 0 vs 3.8), febrile neutropenia (0 vs 1.1 & 3.4 vs 3.4), sepsis (1.2 vs 0 & 0 vs 1.5) and flu-like syndrome (0 vs 1.1 & 0 vs 0.8).
This is the largest database reported to date examining the safety of an IV viral agent. Pelareorep’s administration, in combination with paclitaxel or carboplatin-paclitaxel, is safe and well tolerated. Continued evaluation in a registration trial is planned.
Clinical trial identification
NCI-GOG 0186H (NCT01199263). Ongoing, but not recruiting
NCI-8601 (NCT01280058). Ongoing, but not recruiting NCI- Canada (CCTG)
NCIC-CTG IND.213 (NCT01656538). Ongoing, but not recruiting Oncolytics Biotech Inc:
REO011 – UK (Karapanagiotou et al. CCR 2012) Completed
REO015 (NCT00753038) Completed
REO016 (NCT00861627) Completed
REO018 (NCT01166542). Completed
REO021 (NCT00998192) Completed
Legal entity responsible for the study
Studies were sponsored/conducted by NCI-US, NCI-Canada (CCTG) or Oncolytics Biotech Inc. See section of Clinical Trial Identification
NCI-US and NCI- Canada conducted their own studies and Oncolytics Biotech only provided the drug. Some studies were fully supported and conducted by Oncolytics. Details can be found in the Clinical Trial Identification section
A.A. Gutierrez: Chief Medical Officer and an employee of Oncolytics Biotech Inc. (or one of its affiliated corporations). Own shares in or have options to purchase shares in Oncolytics Biotech Inc. C. Reid: Paid consultant of Oncolytics Biotech. M. Crawford: Employee of Oncolytics Biotech Inc. (or one of its affiliated corporations) and own shares in or have options to purchase shares in Oncolytics Biotech Inc. K. Cheetham, A. Penman, N. Noronha: Employee of Oncolytics Biotech Inc. (or one of its affiliated corporations) and own shares in or have options to purchase shares in Oncolytics Biotech Inc. A. Dzugalo: Employee of Oncolytics Biotech Inc. (or one of its affiliated corporations) and own shares in or have options to purchase shares in Oncolytics Biotech Inc. M. Parsi, D. Galindez, R. O\'Flynn: Paid consultant of Oncolytics Biotech. M. Coffey: President and CEO of Oncolytics Biotech Inc. As an employee of Oncolytics Biotech Inc. (or one of its affiliated corporations) he owns shares in or have options to purchase shares in Oncolytics Biotech Inc.