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 - 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 -