Pelareorep plus atezolizumab for advanced or metastatic gastrointestinal cancers

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 study tests whether adding pelareorep to atezolizumab (with or without chemotherapy) can help people with advanced or metastatic gastrointestinal cancers have better tumor responses.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 122 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oncolytics Biotech (industry)
• Drugs / interventions: chemotherapy
• Locations: 15 sites (Heidelberg, Baden-Wurttemberg and 14 other locations)
• Trial ID: NCT07280377 on ClinicalTrials.gov

What this trial studies

This is an open-label phase 1/2 platform trial enrolling multiple GI cancer cohorts to explore safety, biomarkers, and early signs of efficacy. Patients are assigned to one of five cohorts (cohorts 1–4 non-randomized; cohort 5 randomized 1:1 into two arms) and receive combinations of pelareorep, atezolizumab, and in some cohorts standard chemotherapy regimens. Primary early efficacy endpoints include objective response rate (ORR) for cohorts 1, 2, 4, and 5 and disease control rate (DCR) for cohort 3, with tumor response assessed at week 16 for most cohorts; cohorts use a Simon two-stage design with predefined expansion rules. The trial also measures immune-related biomarkers to test the hypothesis that pelareorep can prime the tumor microenvironment to increase PD-L1 expression and new T cell clones, potentially improving checkpoint inhibitor responses.

Who should consider this trial

Good fit: Adults with advanced or metastatic gastrointestinal cancers who have measurable disease, ECOG performance status 0–1, adequate organ function, and no prior treatment with immune checkpoint inhibitors are the intended candidates.

Not a fit: Patients who have received prior immune checkpoint inhibitors, have uncontrolled infections, symptomatic brain metastases, active severe cardiac or interstitial lung disease, or very recent systemic therapy are unlikely to qualify or benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could increase response rates and potentially improve survival for people with advanced GI cancers who have few effective options.

How similar studies have performed: Early-phase studies of oncolytic viruses combined with PD-1/PD-L1 inhibitors have shown promising signals in some tumor types, but definitive survival benefits in large trials have not yet been established.

Eligibility criteria

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

Where this trial is running

Heidelberg, Baden-Wurttemberg and 14 other locations

• Nationales Centrum für Tumorerkrankungen Heidelberg — Heidelberg, Baden-Wurttemberg, Germany (RECRUITING)
• SLK-Kliniken Heilbronn GmbH — Heilbronn, Baden-Wurttemberg, Germany (RECRUITING)
• Universitätsklinikum Tübingen — Tübingen, Baden-Wurttemberg, Germany (RECRUITING)
• Universitätsklinikum Ulm — Ulm, Baden-Wurttemberg, Germany (RECRUITING)
• Gemeinschaftspraxis Dr. Med Bernhard Heinreich — Augsburg, Bavaria, Germany (RECRUITING)
• Klinikum der Universität München — München, Bavaria, Germany (RECRUITING)
• Hämatologisch-Onkologische Praxis Eppendorf — Hamburg, Free and Hanseatic City of Hamburg, Germany (RECRUITING)
• Asklepios Kliniken Hamburg GmbH — Hamburg, Free and Hanseatic City of Hamburg, Germany (RECRUITING)
• Krankenhaus Nordwest — Frankfurt am Main, Hesse, Germany (RECRUITING)
• St. Josef-Hospìtal, Bochum — Bochum, North Rhine-Westphalia, Germany (RECRUITING)
• Universitätsmedizin Mainz — Mainz, Rhineland-Palatinate, Germany (RECRUITING)
• Caritasklinikum Saarbrücken St. Theresia — Saarbrücken, Saarland, Germany (RECRUITING)
• Klinikum Chemnitz gGmbH — Chemnitz, Saxony, Germany (RECRUITING)
• Universität Leipzig — Leipzig, Saxony, Germany (RECRUITING)
• Charité Universitätsklinikum Berlin — Berlin, State of Berlin, Germany (RECRUITING)

Study contacts

• Study coordinator: Reference Study ID Number: REO 029 GOBLET

Conditions: Anal Cancer Metastatic, Squamous Cell Carcinoma of the Anus Stage Unspecified, Pancreatic Cancer Metastatic, Unresectable Pancreatic Carcinoma