Pelareorep (REOLYSIN) is an immuno oncology viral agent that contains a naturally occurring, ubiquitous, non-enveloped human dearing strain reovirus. Pelareorep selectively replicates in tumor cells harboring gene mutations that downregulate the IFN-induced antiviral response (e.g., KRAS-mutations) which results in their lysis. Pel is synergistic with irinotecan (IRI) in in vitro and in vivo models.
This is a phase I dose escalation study of FOLFIRI/B + Pel. Eligible pts are adults with oxaliplatin refractory KRAS-mutant mCRC. Both, IRI (150-180 mg/m2) and Pel (1x1010 TCID50 to 3x1010 TCID50) were escalated. Pel was given IV over 1 hr days 1-5 every 4 weeks (wk). Primary objectives were to determine toxicity, recommended phase two dose (RPTD), and pharmacokinetics. Secondary objectives were response rate, progression-free and overall survival (PFS and OS). Tumor biopsies post Pel were optional and subject to electron microscopy (EM).
36 pts enrolled; FOLFIRI naïve (24) and pre-treated (12). Common (>10%) grade 3-4 toxicity include: neutropenia, anemia, and thrombocytopenia. At 180 mg/m2 of IRI, among FOLFIRI pretreated pts, 2 had dose-limiting toxicity (DLT) in cycle 1; in FOLFIRI naïve patients, none/6 had a DLT, with a median PFS of 49 wk (range: 10-91 wk). 5 patients are currently on therapy. The RPTD is IRI 180 mg/m2 and Pel 3x1010 TCID50. Of 32 evaluable pts, 3 had a partial response. EM of tumor biopsies showed dying cells with degenerating endoplasmic reticulum, large nonfunctional mitochondria, heterochromatin, condensed DNA, and viral factories, both empty and active. There were discrete holes in the cytoplasm leading to dampening of cellular proliferation. Immunogold staining against viral capsid protein σ demonstrated viral “homing” in the tumor cells. Flow cytometry reveals expansion of dendritic cells with consequent activation of cytotoxic T cells.
The combination was safe, well tolerated, with a PFS (49 wk), superior to historic data (25-30 wk). Detailed PK and immune data will be presented.
Clinical trial identification
Legal entity responsible for the study
Conquer Cancer Foundation
S. Goel: Research Funding from Oncolytics Inc. A. Ocean: Research Funding from Oncolytics Inc. A.A. Gutierrez: Chief Medical Officer of Oncolytics Biotech Inc. 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. Coffey: President and CEO of Oncolytics Biotech Inc. 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. G. Gill: 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. All other authors have declared no conflicts of interest.