Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2017 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
A study of REOLYSIN in combination with pembrolizumab and chemotherapy in patients (pts) with relapsed metastatic adenocarcinoma of the pancreas (MAP).
Gastrointestinal (Noncolorectal) Cancer
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr e15753)
Author(s): Devalingam Mahalingam, Christos Fountzilas, Jennifer L. Moseley, Nicole Noronha, Karol Cheetham, Adrian Dzugalo, Gerard Nuovo, Andres Gutierrez, Sukeshi Patel Arora; Cancer Therapy and Research Center at UT Health Science Center, San Antonio, TX; The University of Texas Health Sciences Center, San Antonio, TX; Institute for Drug Development, Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, TX; Oncolytics Biotech, Calgary, AB, Canada; OSU Comprehensive Cancer Center, Powell, OH
Background: REOLYSIN is an immuno-oncology-reoviral agent that induces an inflamed tumor phenotype secondary to viral infection of cancer cells. In combination with chemotherapy, it achieves 1 & 2 year-survival rates of 46% & 24% in MAP pts, respectively. Tumor analysis from pts showed reovirus protein replication, T-cell infiltration and upregulation of PD-L1. Similarly, the combination of REOLYSIN with anti-PD-1 antibody documented survival benefit in a pre-clinical model. We hypothesized that REOLYSIN in combination with chemo and pembrolizumab in pts with MAP would be clinically efficacious. Methods: A phase 2 study (NCT02620423) enrolled MAP pts who progressed after first line treatment. Pts received REOLYSIN (4.5 x 10 10TCID 50 IV, D1 & D2), plus pembrolizumab (2mg/kg IV, D8) plus either 1)5-FU (LV (200 mg/m2 /5-FU 200 mg /m2 IV bolus, 5-FU 1200mg/m2 continuous IV infusion D1) or 2) gemcitabine (1000 mg/m2 IV, D1), or 3) irinotecan (125 mg/m2 IV, D1) q3w, until disease progression/unacceptable toxicity. The primary endpoint was safety. Secondary objectives included tumor response & evaluation for reovirus replication/immune analysis. We report results of safety cohort analysis. Results: 11 pts were enrolled with REOLYSIN, pembrolizumab and gem (n = 6), 5-FU (n = 3), or iri (n = 2). Grade 1 or 2 TEAEs occurred in all pts: fever (64%), headache (55%), chills (46%), fatigue (46%), dehydration (27%), and nausea (27%). In one pt (gem arm), transient Gr 2 increased transaminases was reported on two occasions. Grade 3 or 4 TEAEs occurred in 8 pts (73%): abdominal pain, anemia, arthralgias, biliary obstruction, chills, DVT, diarrhea, fever, hyperglycemia, leukopenia, myalgias, nausea, neutropenia, pulmonary emboli, vomiting. Of the 5 efficacy evaluable pts, one had PR (6 m duration) and 2 SD (lasting 126 and 221 days). Seven died secondary to PD. On-treatment biopsy show reovirus infection in cancer cells and immune infiltrates. Conclusions: The combination therapy showed manageable safety profiles and antitumor activity in previously treated MAP pts. Further evaluation of anti-tumor activity of REOLYSIN and anti-PD-1 antibody ± chemotherapy combos is planned. Clinical trial information: NCT02620423