Pembrolizumab in combination with the oncolytic virus pelareorep and chemotherapy in patients with advanced pancreatic adenocarcinoma: A phase Ib study a C

Devalingam Mahalingam, Grey A. Wilkinson, Kevin H. Eng, Paul Fields, Patrick Raber, Jennifer L. Moseley, Karol Cheetham, Matt Coffey, Gerard Nuovo, Pawel Kalinski, Bin Zhang, Sukeshi Patel Arora, Christos Fountzilas

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalClinical Cancer Research
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Mahalingam, D., Wilkinson, G. A., Eng, K. H., Fields, P., Raber, P., Moseley, J. L., Cheetham, K., Coffey, M., Nuovo, G., Kalinski, P., Zhang, B., Arora, S. P., & Fountzilas, C. (2020). Pembrolizumab in combination with the oncolytic virus pelareorep and chemotherapy in patients with advanced pancreatic adenocarcinoma: A phase Ib study a C. Clinical Cancer Research, 26(1), 71-81. https://doi.org/10.1158/1078-0432.CCR-19-2078