Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Prediction of response to pelareorep plus pembrolizumab in pancreatic ductal adenocarcinoma (PDAC).
Gastrointestinal (Noncolorectal) Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e15726)
Author(s): Christos Fountzilas, Grey A Wilkinson, Kevin H. Eng, Paul Fields, Sukeshi Patel Arora, Pawel Kalinski, Patrick Raber, Gerard Nuovo, Matthew C. Coffey, Devalingam Mahalingam; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Oncolytics Biotech Inc, Calgary, AB, Canada; Adaptive Biotechnologies, Seattle, WA; UT Health Science Center, San Antonio, TX; Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH; Northwestern University, Chicago, IL
Background: Pelareorep is an oncolytic reovirus that can induce an inflamed T-cell-infiltrated (hot) phenotype in PDAC. In a phase Ib trial, pelareorep was administered in combination with pembrolizumab and chemotherapy in patients (pts) with advanced, pre-treated PDAC. The safety profile was acceptable and efficacy results were encouraging (Mahalingam ASCO GI 2018). Here we present the results of immune analysis in peripheral blood. Methods: Peripheral blood mononuclear cells (PBMCs) were collected on cycle 1 day 1 (C1D1, pre-pelareorep), C1D8 (pre-pembrolizumab) and C2D1 (pre-pelareorep). RNA from PBMCs was analyzed using a customized Nanostring panel. The research-use only immunoSEQ Assay (Adaptive Biotechnologies, Seattle, WA) was used to characterize T-cell receptors from PBMCs. Results: Eleven pts were enrolled. Disease control was achieved in 50% of the 6 efficacy-evaluable pts. One pt achieved PR that lasted 17.4m. Two additional pts achieved SD, lasting 277 and 126 days. Downregulation (relative change < -1.5) of CD1b (C1D1), HLA-C, MAPK14 (C1D8), CD63, LY96, LTF, TXK, TNFSF13, IL25, C1QB (C2D1) and upregulation ( > 1.5) of IL17F (C1D1), MAGEA4, CCL7 (C1D8), CSF1, ICOS, LILRA4, TICAM2 (C2D1) was observed in pts with clinical benefit vs. no clinical benefit (raw p < 0.05). Increase in clonal diversity was noted during therapy overall (Table). C2D1 had significantly more clonal expansion than C1D8; ~30% of expanded clones from C1D8 were also expanded at C2D1 (durable). High numbers of early expanded (C1D8 only) and durable clones were associated with longer survival. Conclusions: Pts with disease control had higher baseline IL17F compared to non-responders. On-treatment relative decrease in IL25 (Th2), increase in LILRA4, TICAM2 (antiviral response) and ICOS were noted in these pts. There was new clone expansion after treatment overall; ~30% of expanded clones at C1D8 were durable. Early and durable clonal expansion correlated with survival. A phase II trial with pelareorep plus pembrolizumab in advanced PDAC is ongoing. Clinical trial information: NCT02620423
|C1D1 mean (range)||C1D8 mean (range)||C2D1 mean (range)|
|T-cell Fraction||0.29 (0.04-0.55)||0.48 (0.26-0.73)||0.39 (0.15-0.68)|
|Morisita Index*||NA||0.82 (0.17-0.99)||0.72 (0.25-0.97)|
|Number Expanded Clones||NA||35.8 (7-131)||131.556 (1-538)|
|Number New Clones Expanded||NA||30.4 (7-105)||114.889 (1-523)|
|Fraction New Clones Observed||NA||0.86 (0.61-1)||0.87 (0.63-1)|
*Composite of clonality/diversity between two samples- if perfectly identical = 1, if completely different = 0, normal variation over a month is ~0.9– 0.95.