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

NCT ID: NCT07280377

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-27
• Study Completion Date: 2028-12-31

Brief Summary

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.

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.

Conditions

Anal Cancer Metastatic; Squamous Cell Carcinoma of the Anus Stage Unspecified; Pancreatic Cancer Metastatic; Unresectable Pancreatic Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Pelareorep

Intervention Type: DRUG

Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion

Atezolizumab

Intervention Type: DRUG

Atezolizumab 840 mg IV infusion

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

Group Type: EXPERIMENTAL

Pelareorep

Intervention Type: DRUG

Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion

Atezolizumab

Intervention Type: DRUG

Atezolizumab 840 mg IV infusion

Trifluridine Tipiracil

Intervention Type: DRUG

Trifluridine/tipiracil administered at a 35 mg/m2 dose orally twice daily

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

Group Type: EXPERIMENTAL

Pelareorep

Intervention Type: DRUG

Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion

Atezolizumab

Intervention Type: DRUG

Atezolizumab 840 mg IV infusion

Cohort 5: Metastatic PDAC 1L

Patients with 1L metastatic PDAC: Pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab

Group Type: EXPERIMENTAL

Pelareorep

Intervention Type: DRUG

Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion

Atezolizumab

Intervention Type: DRUG

Atezolizumab 840 mg IV infusion

mFOLFIRINOX Treatment Regimen

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pelareorep

Intervention Type: DRUG

Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion

Atezolizumab

Intervention Type: DRUG

Atezolizumab 840 mg IV infusion

Gemcitabine and nab-paclitaxel

Intervention Type: DRUG

Gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2)

Interventions

Pelareorep

Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion

Intervention Type: DRUG

Atezolizumab

Atezolizumab 840 mg IV infusion

Intervention Type: DRUG

Gemcitabine and nab-paclitaxel

Gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2)

Intervention Type: DRUG

Trifluridine Tipiracil

Trifluridine/tipiracil administered at a 35 mg/m2 dose orally twice daily

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Gemzar; Abraxane; Lonsurf

Eligibility Criteria

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.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Crolll Gmbh

OTHER

Sponsor Role: collaborator

AIO-Studien-gGmbH

OTHER

Sponsor Role: collaborator

Oncolytics Biotech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nationales Centrum für Tumorerkrankungen Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status: RECRUITING

SLK-Kliniken Heilbronn GmbH

Heilbronn, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Gemeinschaftspraxis Dr. Med Bernhard Heinreich

Augsburg, Bavaria, Germany

Site Status: RECRUITING

Klinikum der Universität München

München, Bavaria, Germany

Site Status: RECRUITING

Hämatologisch-Onkologische Praxis Eppendorf

Hamburg, Hamburg, Germany

Site Status: RECRUITING

Asklepios Kliniken Hamburg GmbH

Hamburg, Hamburg, Germany

Site Status: RECRUITING

Krankenhaus Nordwest

Frankfurt am Main, Hesse, Germany

Site Status: RECRUITING

St. Josef-Hospìtal, Bochum

Bochum, North Rhine-Westphalia, Germany

Site Status: RECRUITING

Universitätsmedizin Mainz

Mainz, Rhineland-Palatinate, Germany

Site Status: RECRUITING

Caritasklinikum Saarbrücken St. Theresia

Saarbrücken, Saarland, Germany

Site Status: RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, Saxony, Germany

Site Status: RECRUITING

Universität Leipzig

Leipzig, Saxony, Germany

Site Status: RECRUITING

Charité Universitätsklinikum Berlin

Berlin, State of Berlin, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Reference Study ID Number: REO 029 GOBLET

Role: CONTACT

reo-029@oncolytics.ca

+1 (858) 247- 7829

Other Identifiers

2024-515936-62-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020-003996-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

REO 029

Identifier Type: -

Identifier Source: org_study_id