Combination of pembrolizumab and pelareorep promotes anti-tumour immunity in advanced pancreatic adenocarcinoma (PDAC)

Devalingam Mahalingam*, Siqi Chen, Ping Xie, Houra Loghmani, Thomas Heineman, Aparna Kalyan, Sheetal Kircher, Irene B. Helenowski, Xinlei Mi, Victoria Maurer, Matt Coffey, Mary Mulcahy, Al Benson, Bin Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915). Methods: PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood. Results: Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8+ T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4+ Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1+ cells touching CD8+ T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR. Conclusion: Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation.

Original languageEnglish (US)
Pages (from-to)782-790
Number of pages9
JournalBritish Journal of Cancer
Issue number5
StatePublished - Sep 21 2023

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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