A Study to Evaluate ATP150/ATP152, VSV-GP154 and Ezabenlimab in Patients With KRAS G12D/G12V Mutated PDAC (KISIMA-02)

Study Overview
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Brief Summary
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The goal of this clinical trial is to test an experimental treatment (immunotherapy) in pancreatic cancer patients. The main research objectives are: to evaluate if the KISIMA-02 treatment is safe and well-tolerated (first part) to evaluate if the KISIMA-02 treatment has an impact on the time to observe a possible reappearance of the tumor (second part) Participants will receive: i) a therapeutic protein vaccine ATP150 or ATP 152 ii) a viral vector VSV-GP154 iii) an immune checkpoint inhibitor Ezabenlimab In the second part of the study, researchers will compare treatment group versus observational group.

Detailed Description
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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. Part A (metastatic and locally advanced PDAC patients) Cohort A: ATP150/ATP152 and VSV-GP154 treatment Part B (locally advanced and resected PDAC patients) Cohort B: ATP150/ATP152, Ezabenlimab and VSV-GP154 treatment Part C (resected PDAC patients) Cohort C: ATP150/ATP152, Ezabenlimab and VSV-GP154 treatment (treatment versus observational arm)

Official Title
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A Phase 1b Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ATP150/ATP152, VSV-GP154 and Ezabenlimab (BI 754091) in Patients With KRAS G12D/G12V Mutated Pancreatic Ductal Adenocarcinoma (KISIMA-02)

Conditions
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Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: VSV-GP154
* Drug: ATP150
* Drug: ATP152
* Drug: Ezabenlimab


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) with KRAS G12D or KRAS G12V mutation. ECOG performance status of 0 or 1. Patients with advanced or metastatic disease who completed at least 16 weeks of standard 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). Life expectancy at least 12 months (resected PDAC), or at least 6 months (advanced/metastatic PDAC). Archival tumor tissue availability for central KRAS analysis. Key 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 (advanced/metastatic PDAC) or 28 (resected PDAC) days from initiation of study treatment. Prior use of immunotherapeutic agents, including but not limited to checkpoint inhibitors or VSV-based agents. Diagnosis of immunodeficiency. Chronic systemic treatment with steroids or other immunosuppressive medications. Active autoimmune disease requiring systemic treatment within the last 2 years. Use of Tamoxifen within 1 month prior to start of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: For Part C: parallel and randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br> | Drug: VSV-GP154<br>* Injection<br>Drug: ATP150<br>* Injection<br>Drug: ATP152<br>* Injection<br>|
| Experimental: Cohort B<br> | Drug: VSV-GP154<br>* Injection<br>Drug: ATP150<br>* Injection<br>Drug: ATP152<br>* Injection<br>Drug: Ezabenlimab<br>* Infusion<br>|
| Experimental: Cohort C Treatment<br> | Drug: VSV-GP154<br>* Injection<br>Drug: ATP150<br>* Injection<br>Drug: ATP152<br>* Injection<br>Drug: Ezabenlimab<br>* Infusion<br>|
| No Intervention: Cohort C Observational<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of dose-limiting toxicity (DLT) | Part A and B | Over at least 35 days | 
| Disease-free survival (DFS), defined as the time from randomization until confirmed relapse or death from any cause, whichever occurs earlier. | Part C | Throughout the study, on average 2.4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving ctDNA clearance | Part C | Up to 12 months | 
| Proportion of patients experiencing ctDNA non-progression | Part C | up to 12 months | 
| Occurrence of dose-limiting toxicity (DLT) | Part C | Throughout the study, up to 7.5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resected PDAC, KISIMA-02, PDAC, ATP150, ATP152, Ezabenlimab, VSV-GP154, Adjuvant setting, Resected pancreatic ductal adenocarcinoma, Metastatic pancreatic ductal adenocarcinoma, Locally advanced pancreatic ductal adenocarcinoma, Metastatic PDAC, LAPC