PELAREOREP for Gastrointestinal cancers|Metastatic colorectal cancer|Pancreatic cancer|Anal squamous cell carcinoma|Pancreatic ductal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- C1: Patients with histologically or cytologically confirmed, locally advanced/metastatic unresectable PDAC who are eligible for 1L SOC chemotherapy with gemcitabine plus nab-paclitaxel\n- C2: Patients with histologically or cytologically confirmed mCRC with MSI-H/dMMR tumors and no prior systemic treatment for metastatic disease.\n- C3: Patients with histologically or cytologically confirmed mCRC, independent of MSI/dMMR status, who failed (and/or did not tolerate) 2 prior lines of treatment, including oxaliplatin, irinotecan, 5-FU, ± targeted agents such as bevacizumab and/or an anti- EGFR antibody who are eligible for 3L SOC chemotherapy with trifluridine/tipiracil\n- C4: Patients with histologically or cytologically confirmed locally advanced/metastatic unresectable SCCA of viral (HPV) or non-viral origin who failed (and/or did not tolerate) prior systemic chemotherapy\n- C5: Histologically or cytologically confirmed mPDAC and eligible for treatment with mFOLFIRINOX. and De novo mPDAC with no prior systemic chemotherapy"}
• {"criterion_text":"- All Cohorts: 1. Provide written informed consent prior to study participation.\n- All Cohorts: 2. Be at least 18 years of age on the day of providing consent.\n- All Cohorts: 3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of start of treatment.\n- All Cohorts: 4. Have evaluable or measurable lesions per RECIST v1.1.\n- All Cohorts: 5. Have adequate organ function at the time of enrollment as defined by: - Absolute neutrophil count ≥1500/mm3 - Platelet count ≥7.5 × 104/mm3 // C5: Platelet count ≥ 100.000/mm3 - Hemoglobin >8 g/dL (blood transfusion >2 weeks before testing is permitted) // C5: Hemoglobin >9 g/dL - Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x the upper limit of normal (ULN; ≤5 x ULN in patients with liver metastasis) - Total bilirubin ≤1.5 x ULN - Creatinine ≤1.5 x ULN// C5: Serumcreatinine ≤1.0 x ULN - C1-C4: Lipase ≤1.5 x ULN// C5: Albumin ≥ 3.0 g/dL - International normalized ratio (INR) ≤1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g. heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring per local SOC will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local SOC.\n- All Cohorts: 6. Have recovered to ≤grade 1 or baseline for all AEs due to previous therapies or surgeries.\n- All Cohorts: 7. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly-effective form(s) of contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 6 months after the last dose of study drug."}

Exclusion criteria

• {"criterion_text":"- C1-C4: 1. Undergone systemic chemotherapy, radiotherapy, or surgery, <4 weeks before study treatment\n- C1-C4: 2. Received previous treatment with immune checkpoint inhibitors\n- C1-C4: 3. Uncontrolled hypertension (systolic blood pressure ≥150 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with hypotensive agents\n- C1-C4: 4. Acute coronary syndrome (including myocardial infarction and unstable angina), and/or a history of coronary angioplasty or stent placement performed within 6 months of enrollment\n- C1-C4: 5. A large amount of pleural effusion or ascites requiring more than weekly drainage\n- C1-C4: 6. A history of (non-infectious) pneumonitis that required steroids or currently active pneumonitis\n- C1-C4: 7. A ≥grade 3 active infection according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.\n- C1-C4: 8. Symptomatic brain metastasis. (Patients with asymptomatic and stable brain metastasis are eligible for study enrollment.)\n- C1-C4: 9. Interstitial lung disease with symptoms or signs of activity\n- C1-C4: 10. In C1, C2, and C3 only: Positive test results for either anti-human immunodeficiency virus (HIV)-1 antibodies, anti-HIV-2 antibodies, antihuman T cell leukemia virus type 1 (HTLV-1) antibodies, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies.* Testing is not required unless deemed necessary by the investigator * Patients who test positive for anti-HBc antibodies or have detectable HBV-DNA will also be excluded In C4 only: Positive test results for either anti-HIV-1 or HIV-2 antibodies if the CD4+ T cell is <300 cells/μl.* Testing for HIV status is required * To be eligible, HIV+ patients must have an undetectable viral load and be receiving highly active antiretroviral therapy (HAART). Patients must be on established HAART therapy for at least 4 weeks prior to study entry\n- C1-C4: 11. Autoimmune disease that has required systemic treatment in the past 2 years with disease modifying agents, corticosteroids, or immunosuppressive drugs. [Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment]\n- C1-C4: 12. A history or findings of ≥grade 3 congestive heart failure according to the New York Heart Association functional classification.\n- C1-C4: 13. A seizure disorder that requires pharmacotherapy\n- C1-C4: 14. Proteinuria ≥grade 3 (using spot testing; if grade 3, repeat with midstream urine; if still grade 3, then urine collection for 24 hours to confirm grade) as per NCI CTCAE\n- C1-C4: 15. A medical contraindication to undergoing biopsies\n- C1-C4: 16. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation\n- C1-C4: 17. A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug.\n- C1-C4: 18. Women who are pregnant or breastfeeding\n- C1-C4: 19. A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug\n- C1-C4: 20. Any vaccine during screening and the first cycle of treatment\n- C1-C4: 21. Legal incapacity or limited legal capacity"}
• {"criterion_text":"- C5: 1. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic PDAC. Palliative radiotherapy for pain control of metastatic bone lesions is allowed\n- C5: 2. Received previous treatment with immune checkpoint inhibitors\n- C5: 3. History of allergy or known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation, and/or contraindication to any of the study treatments (as outlined in local prescribing information)\n- C5: 4. Known low or absent dihydropyrimidine dehydrogenase (DPD) activity\n- C5: 5. Uncontrolled or severe cardiac disease (history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the prior 6 months), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation)\n- C5: 6. Women currently pregnant or breastfeeding\n- C5: 7. Active, uncontrolled infections\n- C5: 8. Symptomatic brain metastasis\n- C5: 9. Known leptomeningeal disease.\n- C5: 10. History of interstitial lung disease\n- C5: 11. Known active HIV, Hepatitis B (HBV) or Hepatitis C (HCV) infection\n- C5: 12. Active, known, or suspected autoimmune disease\n- C5: 13. Receiving immunosuppressive or myelosuppressive medications that would increase the risk of serious neutropenic complications\n- C5: 14. Seizure disorder that requires pharmacotherapy\n- C5: 15. A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug\n- C5: 16. Any vaccine within 28 days prior to first study treatment or during the first cycle of treatment\n- C5: 17. History of another primary cancer within the last 3 years"}

Primary endpoints

• {"endpoint_text":"- ORR (CR, PR) assessed by the investigator according to RECIST v1.1 at week 16 (within each cohort) cohort 5 (Phase 1b) Safety: To evaluate the safety and tolerability of 1) mFOFIRINOX plus pelareorep and atezolizumab (Arm A) and 2) mFOLFIRINOX plus pelareorep (Arm B). Efficacy: To evaluate the response to treatment measured by ORR in 1) patients treated with mFOLFIRINOX plus pelareorep and atezolizumab (Arm A) and 2) patients treated with mFOLFIRINOX plus pelareorep (Arm B).","definition_or_measurement_approach":"ORR (CR, PR) assessed by the investigator according to RECIST v1.1 at week 16; efficacy measured as objective response rate (complete response, partial response) per RECIST v1.1; safety/tolerability assessed for specified arms."}

Secondary endpoints

• {"endpoint_text":"- PFS defined as the duration from the date of enrollment to the date of progressive disease or death from any cause.","definition_or_measurement_approach":"Progression-free survival (PFS): time from date of enrollment to date of progressive disease or death from any cause."}
• {"endpoint_text":"- OS defined as the time from randomization to death from any cause.","definition_or_measurement_approach":"Overall survival (OS): time from randomization to death from any cause."}
• {"endpoint_text":"- Safety assessments from enrollment to 90 days after last dose of study treatment will include: - Serious and non-serious AEs (clinical and laboratory), laboratory parameters, treatment exposure (total delivered dose and dose modifications), and reasons for treatment discontinuation.","definition_or_measurement_approach":"Safety assessments: collection of serious and non-serious adverse events (clinical and laboratory), laboratory parameters, treatment exposure metrics (total delivered dose, dose modifications), and reasons for discontinuation, from enrollment until 90 days after last dose."}

Germany

Earliest CTIS Part Ii Submission Date

04-10-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

584

Number Of Sites

17

Number Of Participants

102

Primary sponsor

Full Name

Oncolytics Biotech Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Canada