A study of pelareorep in combination with pembrolizumab and chemotherapy in patients (pts) with relapsed metastatic adenocarcinoma of the pancreas (MAP)

Autor: Devalingam Mahalingam, Christos Fountzilas, Jennifer L. Moseley, Nicole Noronha, Karol Cheetham, Adrian Dzugalo, Gerard Nuovo, Andres Gutierrez, Sukeshi Patel Arora
Rok vydání: 2018
Předmět:
Zdroj: Journal of Clinical Oncology. 36:283-283
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2018.36.4_suppl.283
Popis: 283 Background: Pelareorep (REOLYSIN) is a immuno-oncolytic virus (IOV) 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 pelareorep with anti-PD-1 antibody documented survival benefit in a pre-clinical model. We hypothesized that pelareorep in combination with chemo and pembrolizumab in pts with MAP would be clinically efficacious. Methods: A phase 1b study enrolled MAP pts who progressed after first line treatment. Pts received pelareorep (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. Results: 11 pts were enrolled with pelareorep, pembrolizumab and gem (n = 6), 5-FU (n = 3), or iri (n = 2). Most common grade 1 or 2 TEAEs include: fever (73%), headache (55%), chills (46%), dehydration (36%), fatigue (27%) and anemia (27%). 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, urinary tract infection and vomiting. Of the 5 efficacy evaluable pts, one had PR (13.8 m duration) and 2 SD (lasting 126 and 277 days). Eight 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 pelareorep and anti-PD-1 antibody ± chemotherapy combos is planned. Clinical trial information: NCT02620423.
Databáze: OpenAIRE
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