Article Text

Download PDFPDF

650 Pelareorep combined with atezolizumab and chemotherapy demonstrates encouraging results as first-line treatment in advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) patients – interim results from the GOBLET study
  1. Dirk Arnold1,
  2. Maike Collienne1,
  3. Alexander Stein2,
  4. Guy Ungerechts3,
  5. Eray Goekkurt2,
  6. Jack Chater4,
  7. Houra Loghmani5,
  8. Matt Coffey5,
  9. Richard Trauger5,
  10. Uwe Martens6 and
  11. Thomas Heineman5
  1. 1Asklepios Tumorzentrum Hamburg, Hamburg, Germany
  2. 2Hematology-Oncology Practice Eppendorf, Hamburg, Germany
  3. 3University Hospital Heidelberg, Heidelberg, Germany
  4. 4Klinikum Chemnitz gGmbH, Chemnitz, Germany
  5. 5Oncolytics Biotech, Calgary, Canada
  6. 6SLK-Kliniken Heilbronn GmbH, Heilbronn, Germany


Background Pelareorep (pela) is an intravenously administered, non-genetically modified oncolytic reovirus that selectively kills tumor cells and activates both innate and adaptive immune responses. In prior clinical trials, pela was shown to prime tumors for checkpoint inhibition by enhancing infiltration of lymphocytes into tumors and increasing PD-L1 expression. The GOBLET basket study was designed to assess the safety and efficacy of pela in combination with atezolizumab (atezo) +/- chemotherapy in multiple gastrointestinal cancer indications (PDAC, 1L MSI-H colorectal cancer, 3L MSS colorectal cancer, 2L anal carcinoma). Here we report the interim results for patients with advanced/metastatic PDAC.

Methods GOBLET is a phase 1/2 Simon two-stage study. PDAC patients enrolled in GOBLET are treated with pela, atezo and gemcitabine/nab-paclitaxel. They must have locally advanced/metastatic unresectable disease evaluable by RECIST v1.1, be ≥18 years old and have an ECOG score ≤1. The first stage enrolled 12 evaluable PDAC patients (evaluable patients must have at least one post-baseline tumor assessment). The primary objectives are safety and efficacy by investigator-assessed objective response rate (ORR). The protocol-specified Stage 1 success criterion for PDAC is ≥3 confirmed responses. In addition, blood samples collected at baseline (cycle 1 day 1 [c1d1]) and c2d1 of the 28-day treatment cycle will undergo T-cell receptor sequencing (TCR-seq) to assess treatment effect on the T-cell repertoire.

Results No safety signals have been observed in patients treated with pela, atezo and gemcitabine/nab-paclitaxel. Seven of 10 evaluable patients to date (28July2022) had a partial response at week 8 or later (3 confirmed, 4 currently unconfirmed), and 2 had stable disease for an objective response rate (ORR) of 70% and a clinical benefit rate (CBR) of 90%. TCR-seq revealed an expansion of T-cell clones, a decrease in clonal diversity, and an increase in T-cell fraction from c1d1 to c2d1 in all three patients for whom data are available. Updated tumor response and TCR-seq results will be presented.

Conclusions Consistent with previous studies in PDAC and other indications, pela in combination with chemotherapy and a checkpoint inhibitor is well-tolerated. The primary efficacy success criterion was met, and the high ORR and CBR observed in this study are very encouraging in comparison to tumor response rates observed in prior first-line PDAC treatment studies. The changes in T-cell repertoire observed in the first three patients are consistent with previous pelareorep/checkpoint inhibitor studies and will be further evaluated as possible biomarkers for response to therapy.

Trial Registration (Eudra-CT: 2020-003996-16)

Ethics Approval The study was approved by the ethic committee of Hamburg on February 22, 2021.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.