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

8 Scopus citations

Abstract

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
Volume129
Issue number5
DOIs
StatePublished - Sep 21 2023

Funding

DM received research funding Oncolytics Biotech and drug support from Merck. HL, TH and MC are employees of Oncolytics Biotech. The study received Pembrolizumab from Merck (MISP 55500). The study received Reolysin and research funding from Oncolytics Biotech.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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