A Phase 1b Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of a Heterologous Prime Boost Vaccination (ATP150/ATP152/ATP162, VSV-GP154) and Ezabenlimab (BI 754091) in Patients With Pancreatic Ductal Adenocarcinoma.
Overview
- Phase
- Phase 1
- Intervention
- ATP152
- Conditions
- Not specified
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 58
- Locations
- 24
- Primary Endpoint
- Occurrence of dose-limiting toxicity (DLT)
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
This study is open to adults with advanced pancreatic cancer. The study tests a type of immunotherapy. It is a protein treatment combined with a virus that may kill cancer cells and help the immune system fight cancer. The immunotherapy is combined with a study medicine called ezabenlimab. Ezabenlimab is an antibody that may also help the immune system fight cancer.
The purpose is to find the highest dose of the immunotherapy that people with pancreatic cancer can tolerate when taken alone or together with ezabenlimab (Part A and B). To find out, researchers look at the number of participants with certain severe health problems. The purpose of Part C is to check whether the immunotherapy combined with ezabenlimab may increase survival. Participants are put randomly into 2 groups. One group receives the immunotherapy combined with ezabenlimab and the other group receives standard treatment. Researchers compare the results between the groups.
Participants can stay in the study as long as they tolerate the treatment or up to 1 year. During that time, they regularly visit the site. At all visits, the doctors closely check the health of the participants and note any severe health problems.
Detailed Description
This is an open-label, phase 1b study to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of a heterologous prime-boost vaccine (protein and viral vector) regimen without/with the PD-1 inhibitor Ezabenlimab. COMPLETED - Part A (metastatic and locally advanced PDAC patients) Cohort A: ATP150/ATP152 and VSV-GP154 treatment ONGOING - Part B (locally advanced and resected PDAC patients) Cohort B: ATP150/ATP152, Ezabenlimab and VSV-GP154 treatment Cohort B1, B2, B3, B4: dose escalation NOT STARTED YET - Part C (resected PDAC patients) Cohort C: ATP162, and VSV-GP154 treatment in combination with Ezabenlimab. (treatment versus observational arm)
Investigators
CT Disclosure and Data Transparency
Scientific
Boehringer Ingelheim International GmbH
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC)
- •ECOG performance status of 0 or
- •Patients with advanced or metastatic disease who completed at least 16 weeks of standard of care systemic chem-/chemoradiotherapy and achieved a partial response or stable disease.
- •Patients who underwent confirmed R0 or R1 resection and completed at least 3 months of combined peri-adjuvant multiagent chemotherapy.
- •No evidence of disease progression or recurrence.
- •Start of study treatment within 12 weeks from the last curative treatment (resected PDAC).
- •Patient must have completed 8-12 cycles of FOLFIRINOX or mFOLFIRINOX either as adjuvant, neoadjuvant, or perioperative (Part C)
- •Life expectancy at least 12 months (resected PDAC), or at least 6 months (advanced/metastatic PDAC).
- •Archival tumor tissue availability for central KRAS analysis and research.
Exclusion Criteria
- •Not yet recovered from surgery (resected PDAC).
- •Gastro-intestinal bowel obstruction.
- •Other malignancy within the last 3 years.
- •Prior chemotherapy or targeted small molecule therapy within 14 (locally advanced/metastatic PDAC) or 28 (resected PDAC) days from initiation of study treatment.
- •Prior radiotherapy within 14 days (advanced/metastatic PDAC). No prior radiotherapy. in resected PDAC
- •Prior use of immunotherapeutic agents, including but not limited to checkpoint inhibitors or VSV-based agents.
- •Diagnosis of immunodeficiency, and/or history of allogeneic organ transplant
- •Chronic systemic treatment with steroids or other immunosuppressive medications.
- •Active autoimmune disease requiring systemic treatment within the last 2 years.
- •Chronic or concurrent active infectious disease requiring systemic antibodies, antifungal, or antiviral treatment
Arms & Interventions
Cohort B
Intervention: ATP152
Cohort B
Intervention: Ezabenlimab
Cohort C Treatment
Intervention: VSV-GP154
Cohort C Treatment
Intervention: Ezabenlimab
Cohort C Treatment
Intervention: ATP162
Cohort A
Intervention: VSV-GP154
Cohort A
Intervention: ATP150
Cohort A
Intervention: ATP152
Cohort B
Intervention: VSV-GP154
Cohort B
Intervention: ATP150
Cohort C Observational
Outcomes
Primary Outcomes
Occurrence of dose-limiting toxicity (DLT)
Time Frame: Over at least 35 days
Part A and B
Disease-free survival (DFS), defined as the time from randomization until confirmed relapse or death from any cause, whichever occurs earlier.
Time Frame: Through study completion, an average of 24 months.
Part C
Secondary Outcomes
- Proportion of patients with clearance and normalization of tumor biomarkers(Up to 12 months)
- Occurrence of dose-limiting toxicity (DLT) during the on-treatment period(Throughout the study, up to 12 months.)