TY - JOUR
T1 - Pembrolizumab in combination with the oncolytic virus pelareorep and chemotherapy in patients with advanced pancreatic adenocarcinoma
T2 - A phase Ib study a C
AU - Mahalingam, Devalingam
AU - Wilkinson, Grey A.
AU - Eng, Kevin H.
AU - Fields, Paul
AU - Raber, Patrick
AU - Moseley, Jennifer L.
AU - Cheetham, Karol
AU - Coffey, Matt
AU - Nuovo, Gerard
AU - Kalinski, Pawel
AU - Zhang, Bin
AU - Arora, Sukeshi Patel
AU - Fountzilas, Christos
N1 - Funding Information:
Oncolytics Biotech Inc. provided pelareorep and partial funding. The correlative studies were partially funded by a grant provided by the Roswell Park Alliance Foundation. C. Fountzilas was a recipient of a Cancer Research Training Award (RP 140105) funded by the Cancer Prevention & Research Institute of Texas. This work was supported by NCI grant P30CA016056 involving the use of Roswell Park Comprehensive Cancer Center's Genomic Shared Resource. Luminex cytokine analysis services were provided by the Flow and Image Cytometry Core facility at the Roswell Park Comprehensive Cancer Center, which is supported in part by the NCI Cancer Center Support Grant P30CA016056. SPA: NIH CA054174, NIA AG044271.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose: Pelareorep is an intravenously delivered oncolytic reovirus that can induce a T-cell–inflamed phenotype in pancreatic ductal adenocarcinoma (PDAC). Tumor tissues from patients treated with pelareorep have shown reovirus replication, T-cell infiltration, and upregulation of PD-L1. We hypothesized that pelareorep in combination with pembrolizumab and chemotherapy in patients with PDAC would be safe and effective. Patients and Methods: A phase Ib single-arm study enrolled patients with PDAC who progressed after first-line treatment. Patients received pelareorep, pembrolizumab, and either 5-fluoro-uracil, gemcitabine, or irinotecan until disease progression or unacceptable toxicity. Study objectives included safety and dose-limiting toxicities, tumor response, evaluation for reovirus replication, and immune analysis in peripheral blood and tumor biopsies. Results: Eleven patients were enrolled. Disease control was achieved in three of the 10 efficacy-evaluable patients. One patient achieved partial response for 17.4 months. Two additional patients achieved stable disease, lasting 9 and 4 months, respectively. Treatment was well tolerated, with mostly grade 1 or 2 treatment-related adverse events, including flu-like symptoms. Viral replication was observed in on-treatment tumor biopsies. T-cell receptor sequencing from peripheral blood revealed the creation of new T-cell clones during treatment. High peripheral clonality and changes in the expression of immune genes were observed in patients with clinical benefit. Conclusions: Pelareorep and pembrolizumab added to chemotherapy did not add significant toxicity and showed encouraging efficacy. Further evaluation of pelareorep and anti–PD-1 therapy is ongoing in follow-up studies. This research highlights the potential utility of several pretreatment and on-treatment biomarkers for pelareorep therapy warranting further investigation.
AB - Purpose: Pelareorep is an intravenously delivered oncolytic reovirus that can induce a T-cell–inflamed phenotype in pancreatic ductal adenocarcinoma (PDAC). Tumor tissues from patients treated with pelareorep have shown reovirus replication, T-cell infiltration, and upregulation of PD-L1. We hypothesized that pelareorep in combination with pembrolizumab and chemotherapy in patients with PDAC would be safe and effective. Patients and Methods: A phase Ib single-arm study enrolled patients with PDAC who progressed after first-line treatment. Patients received pelareorep, pembrolizumab, and either 5-fluoro-uracil, gemcitabine, or irinotecan until disease progression or unacceptable toxicity. Study objectives included safety and dose-limiting toxicities, tumor response, evaluation for reovirus replication, and immune analysis in peripheral blood and tumor biopsies. Results: Eleven patients were enrolled. Disease control was achieved in three of the 10 efficacy-evaluable patients. One patient achieved partial response for 17.4 months. Two additional patients achieved stable disease, lasting 9 and 4 months, respectively. Treatment was well tolerated, with mostly grade 1 or 2 treatment-related adverse events, including flu-like symptoms. Viral replication was observed in on-treatment tumor biopsies. T-cell receptor sequencing from peripheral blood revealed the creation of new T-cell clones during treatment. High peripheral clonality and changes in the expression of immune genes were observed in patients with clinical benefit. Conclusions: Pelareorep and pembrolizumab added to chemotherapy did not add significant toxicity and showed encouraging efficacy. Further evaluation of pelareorep and anti–PD-1 therapy is ongoing in follow-up studies. This research highlights the potential utility of several pretreatment and on-treatment biomarkers for pelareorep therapy warranting further investigation.
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U2 - 10.1158/1078-0432.CCR-19-2078
DO - 10.1158/1078-0432.CCR-19-2078
M3 - Article
C2 - 31694832
AN - SCOPUS:85077475533
SN - 1078-0432
VL - 26
SP - 71
EP - 81
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -