A phase 1/2 multiple-indication biomarker, safety, and efficacy study in advanced or metastatic Gastrointestinal cancers exploring treatment comBinations with peLarEorep and aTezolizumab (GOBLET)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncolytics Biotech Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Oct 2024 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Oncolytics Biotech, Inc.

External identifiers

EU CT number

2024-515936-62-00

EudraCT number

2020-003996-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Cohort 1 and Cohort 3, Phase 1b and Phase 2:
The tolerability of pelareorep plus atezolizumab in combination with SOC chemotherapy.
Cohort 1, Phase 2:
The tolerability of the combination of pelareorep plus atezolizumab in combination with SOC chemotherapy and the response to treatment
measured by ORR at week 16 in pat. treated with pelareorep plus atezolizumab in combination with SOC chemotherapy.
Cohort 3, Phase 2:
The tolerability of pelareorep plus in combination with SOC chemotherapy and the response to treatment measured by DCR at week 16 in pat. treated with pelareorep plus atezolizumab in combination with
SOC chemotherapy.
Cohort 2 and Cohort 4, Phase 2:
The response to treatment measured by ORR at week 16 in pat. treated with pelareorep plus atezolizumab in combination with SOC chemotherapy and the tolerability of the combination of pelareorep plus
atezolizumab.
The response to treatment measured by ORR at week 16 in pat. treated with pelareorep plus atezolizumab.

Secondary objectives 3

1. Cohort 1 and Cohort 3, Phase 1b: There are no secondary objectives in the Phase 1b part of Cohort 1 and Cohort 3
2. Cohort 1 and Cohort 3, Phase 2: Efficacy To assess the anti-tumor activity of the treatment combinations based on: Progression-free survival (PFS), Overall survival (OS), Duration of response (DOR) and Overall disease control rate (DCR) [Note that PFS and OS data from patients enrolled during Phase 1b of Cohort 1 (Safety Run-in) will be included in the efficacy analysis at the end of Stage 1 Phase 2].
3. Cohort 2 and Cohort 4, Phase 2: Efficacy To assess the anti-tumor activity of the treatment combinations based on: Progression-free survival (PFS), Overall survival (OS), Duration of response (DOR) and Overall disease control rate (DCR)

Conditions and MedDRA coding

Patients with advanced or metastatic gastrointestinal (GI) tumors.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Cohort-specific criteria: C1: Patients with histologically or cytologically confirmed, locally advanced/metastatic unresectable PDAC who are eligible for 1L SOC chemotherapy with gemcitabine plus nab-paclitaxel C2: Patients with histologically or cytologically confirmed mCRC with MSI-H/dMMR tumors and no prior systemic treatment for metastatic disease. 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 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 C5: Histologically or cytologically confirmed mPDAC and eligible for treatment with mFOLFIRINOX. and De novo mPDAC with no prior systemic chemotherapy
2. All Cohorts: 1. Provide written informed consent prior to study participation. 2. Be at least 18 years of age on the day of providing consent. 3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of start of treatment. 4. Have evaluable or measurable lesions per RECIST v1.1. 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. 6. Have recovered to ≤grade 1 or baseline for all AEs due to previous therapies or surgeries. 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 2

1. C1-C4: 1. Undergone systemic chemotherapy, radiotherapy, or surgery, <4 weeks before study treatment 2. Received previous treatment with immune checkpoint inhibitors 3. Uncontrolled hypertension (systolic blood pressure ≥150 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with hypotensive agents 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 5. A large amount of pleural effusion or ascites requiring more than weekly drainage 6. A history of (non-infectious) pneumonitis that required steroids or currently active pneumonitis 7. A ≥grade 3 active infection according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. 8. Symptomatic brain metastasis. (Patients with asymptomatic and stable brain metastasis are eligible for study enrollment.) 9. Interstitial lung disease with symptoms or signs of activity 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 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] 12. A history or findings of ≥grade 3 congestive heart failure according to the New York Heart Association functional classification. 13. A seizure disorder that requires pharmacotherapy 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 15. A medical contraindication to undergoing biopsies 16. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation 17. A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug. 18. Women who are pregnant or breastfeeding 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 20. Any vaccine during screening and the first cycle of treatment 21. Legal incapacity or limited legal capacity
2. 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 2. Received previous treatment with immune checkpoint inhibitors 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) 4. Known low or absent dihydropyrimidine dehydrogenase (DPD) activity 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) 6. Women currently pregnant or breastfeeding 7. Active, uncontrolled infections 8. Symptomatic brain metastasis 9. Known leptomeningeal disease. 10. History of interstitial lung disease 11. Known active HIV, Hepatitis B (HBV) or Hepatitis C (HCV) infection 12. Active, known, or suspected autoimmune disease 13. Receiving immunosuppressive or myelosuppressive medications that would increase the risk of serious neutropenic complications 14. Seizure disorder that requires pharmacotherapy 15. A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug 16. Any vaccine within 28 days prior to first study treatment or during the first cycle of treatment 17. History of another primary cancer within the last 3 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 2

1. Efficacy: - PFS defined as the duration from the date of enrollment to the date of progressive disease or death from any cause. - OS defined as the time from randomization to death from any cause.
2. - 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oncolytics Biotech Inc.

Sponsor organisation

Oncolytics Biotech Inc.

Address

804-322 11 Avenue South West

City

Calgary

Postcode

T2R 0C5

Country

Canada

Scientific contact point

Organisation

Oncolytics Biotech Inc.

Contact name

Prof. Dr. Dirk Arnold

Public contact point

Organisation

Oncolytics Biotech Inc.

Contact name

Dr. Thomas Heineman

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications