A Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab (GOBLET)

A Phase 1 / 2 Multiple-indication Biomarker, Safety, and Efficacy Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab

This is an open-label, phase 1/2, multiple-indication platform study to explore safety, potential predictive immune-related biomarkers, and early efficacy (as measured by objective response rate [ORR; Cohorts 1,2, 4,and 5] and disease control rate [DCR; Cohort 3]) in patients with advanced or metastatic gastrointestinal (GI) tumors. Cohorts 1-4 are not randomized; however, Cohort 5 is comprised of two treatment arms to which patients are randomized in a 1:1 ratio.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer Metastatic; Unresectable Pancreatic Carcinoma; Anal Cancer Metastatic; Squamous Cell Carcinoma of the Anus Stage Unspecified
• Intervention / Treatment: Drug: Pelareorep; Drug: Atezolizumab; Drug: Gemcitabine and nab-paclitaxel; Drug: Trifluridine Tipiracil; Drug: mFOLFIRINOX Treatment Regimen

Detailed Description

The overall aim is to assess safety, predictive biomarkers, and preliminary efficacy as assessed by tumor response criteria at week 16 for cohorts1, 2, 3, and 4, and best overall response rate and OS in Cohort 5. If a cohort shows a promising ORR in Stage 1 of the Simon two-stage design, that cohort may be expanded to enroll additional patients (up to 50 patients in Cohorts 1 and 3 , up to 28 patients in Cohort 4, and up to 64 patients in Cohort 5) in an extension phase per predetermined statistical conditions. In addition, either or both arms of Cohort 5 may expand if the data collected in Stage 1 suggest that expansion may help in assessing the potential survival benefit of the investigational therapy(ies). In this study, we hypothesize that treatment with pelareorep will prime the tumor microenvironment (TME) for checkpoint blockade therapy, thereby increasing PD-L1 expression and the number of new T cell clones within the tumor, both of which are associated with increased response to checkpoint blockade.

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Nationales Centrum für Tumorerkrankungen Heidelberg
    • Heilbronn, Baden-Wurttemberg, Germany, 74078
      • SLK-Kliniken Heilbronn GmbH
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Universitätsklinikum Tübingen
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitatsklinikum Ulm
  • Bavaria
    • Augsburg, Bavaria, Germany, 86150
      • Gemeinschaftspraxis Dr. Med Bernhard Heinreich
    • München, Bavaria, Germany, 81377
      • Klinikum der Universität München
  • Free and Hanseatic City of Hamburg
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20249
      • Hämatologisch-Onkologische Praxis Eppendorf
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 22763
      • Asklepios Kliniken Hamburg GmbH
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • Krankenhaus Nordwest
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44791
      • St. Josef-Hospìtal, Bochum
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin Mainz
  • Saarland
    • Saarbrücken, Saarland, Germany, 66113
      • Caritasklinikum Saarbrücken St. Theresia
  • Saxony
    • Chemnitz, Saxony, Germany, 09116
      • Klinikum Chemnitz gGmbH
    • Leipzig, Saxony, Germany, 04103
      • Universität Leipzig
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Charité Universitätsklinikum Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Cohorts 1-5 Inclusion Criteria:

• ECOG performance status of 0 or 1
• Have measurable lesions per RECIST v1.1
• Patients must have adequate hematological, renal, and hepatic function
• Have recovered to ≤grade 1 or baseline for all adverse events (AEs) due to previous therapies or surgeries.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use a highly-effective form(s) of contraception and to continue its use for 6 months after the last dose of study drug.

Exclusion Criteria:

• Undergone systemic chemotherapy, radiotherapy, or surgery, <4 weeks before study treatment.
• Received previous treatment with immune checkpoint inhibitors
• Uncontrolled or severe cardiac disease
• Active, uncontrolled infections
• Symptomatic brain metastasis
• Interstitial lung disease with symptoms or signs of activity.
• Autoimmune disease that has required systemic treatment in the past 2 years with disease modifying agents, corticosteroids, or immunosuppressive drugs.
• A seizure disorder that requires pharmacotherapy.
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
• A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug.
• Women who are pregnant or breastfeeding.
• A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy
• Any vaccine within 28 days prior to first treatment or during the first cycle of study treatment.

Exclusion Criteria:

• In Cohort 1, 2, 3, 4: Life expectancy less than 3 months
• In Cohort 1, 2, 3: known active Hepatitis B (HBV) or Hepatitis C (HCV) infection that requires anti-viral treatment.
• In Cohort 4: Prior HIV infection if the CD4+ T cell is <300 cells/µl
• In Cohort 5: Known low or absent dihydropyrimidine dehydrogenase (DPD) activity.
• In Cohort 5: Known leptomeningeal disease.
• In Cohort 5: History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Metastatic Pancreatic Cancer 1L; Patients with first-line (1L) locally advanced/metastatic unresectable pancreatic ductal adenocarcinoma (PDAC): Pelareorep and atezolizumab added to gemcitabine and nab-paclitaxel	Drug: Pelareorep; Pelareorep 4.5 x 10^10 TCID50 via 1-hour IV infusion; Drug: Atezolizumab; Atezolizumab 840 mg IV infusion; Other Names: Tecentriq; Drug: Gemcitabine and nab-paclitaxel; Gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2); Other Names: Gemzar; Abraxane
Experimental: Cohort 2: Metastatic Colorectal Cancer 1L (MSI-H/dMMR); Patients with 1L metastatic colorectal cancer (mCRC), limited to microsatellite instability-high (MSIH) or mismatch repair deficient (dMMR) tumors: Pelareorep and atezolizumab	Drug: Pelareorep; Pelareorep 4.5 x 10^10 TCID50 via 1-hour IV infusion; Drug: Atezolizumab; Atezolizumab 840 mg IV infusion; Other Names: Tecentriq
Experimental: Cohort 3: Metastatic Colorectal Cancer 3L; Patients with third-line (3L) mCRC independent of microsatellite instability (MSI)/dMMR status: Pelareorep and atezolizumab added to trifluridine/tipiracil	Drug: Pelareorep; Pelareorep 4.5 x 10^10 TCID50 via 1-hour IV infusion; Drug: Atezolizumab; Atezolizumab 840 mg IV infusion; Other Names: Tecentriq; Drug: Trifluridine Tipiracil; Trifluridine/tipiracil administered at a 35 mg/m2 dose orally twice daily; Other Names: Lonsurf
Experimental: Cohort 4: Metastatic Unresectable Anal Cancer >/=2L; Patients with >/= 2L locally advanced/metastatic unresectable squamous cell carcinoma of the anal canal (SCCA) of viral or non-viral origin after prior systemic chemotherapy: Pelareorep and atezolizumab	Drug: Pelareorep; Pelareorep 4.5 x 10^10 TCID50 via 1-hour IV infusion; Drug: Atezolizumab; Atezolizumab 840 mg IV infusion; Other Names: Tecentriq
Experimental: Cohort 5: Metastatic PDAC 1L; Patients with 1L metastatic PDAC: Pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab	Drug: Pelareorep; Pelareorep 4.5 x 10^10 TCID50 via 1-hour IV infusion; Drug: Atezolizumab; Atezolizumab 840 mg IV infusion; Other Names: Tecentriq; Drug: mFOLFIRINOX Treatment Regimen; mFOLFIRINOX- IV oxaliplatin 85 mg/m2; IV leucovorin 400 mg/m2; IV irinotecan 150 mg/m2; 5-FU 2400 mg/m2 by 46-hour infusion, per local standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) for Cohort 1, 2, 4, and 5	Proportion of patients with complete response [CR], partial response [PR] assessed by the investigators and/or central reader according to RECIST v1.1	At week 16 (within each cohort)
Disease Control Rate (DCR) - Cohort 3	DCR (complete response [CR], partial response [PR], and stable disease [SD]) assessed by the investigators according to RECIST v 1.1.	at week 16
Overall Survival (OS) - Cohort 5	OS is defined as the time from date of first treatment to death from any cause	Cohort 5: From the date of randomization through long term follow up at 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from the first dose date of study treatment to the date of investigator-determined objective progression (according to RECIST 1.1) or death from any cause, whichever occurs first.	From initiation of treatment to objective progression or death from any cause, whichever occurs first, up to two years
Duration of Response (DOR)	Time from documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death.	From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years
Disease Control Rate (DCR)	Overall DCR, defined as the number of patients with a best overall response of CR, PR, or SD according to RECIST v. 1.1.	From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years
Overall Response Rate (ORR) - Cohort 1-4	ORR, defined as the percentage of patients with a best overall response of complete response [CR] or partial response [PR] according to RECIST v 1.1, and confirmed ORR, defined as the percentage of patients with a CR or PR at two or more consecutive evaluation timepoints.	From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years
Overall Survival (OS) - Cohort 1-4	OS defined as the time from date of first treatment to death from any cause	From the date of randomization through long term follow up at 3 years

Collaborators and Investigators

• Sponsor: Oncolytics Biotech
• Collaborators: AIO-Studien-gGmbH; Crolll Gmbh

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: December 3, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Albumins; Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; trifluridine tipiracil drug combination; atezolizumab; 130-nm albumin-bound paclitaxel; reolysin
• Other Study ID Numbers: REO 029; 2024-515936-62-00 (Ctis); 2020-003996-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No