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

Sponsor

Amal Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05846516

Collaborator

Boehringer Ingelheim (Industry)

Enrollment

Location

Arms

47.6

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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:

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Ductal Adenocarcinoma	Drug: VSV-GP154 Drug: ATP150 Drug: ATP152 Drug: Ezabenlimab	Phase 1

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.

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)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

85 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

For Part C: parallel and randomizedFor Part C: parallel and randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Mar 13, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A	Drug: VSV-GP154 Injection Drug: ATP150 Injection Drug: ATP152 Injection
Experimental: Cohort B	Drug: VSV-GP154 Injection Drug: ATP150 Injection Drug: ATP152 Injection Drug: Ezabenlimab Infusion
Experimental: Cohort C Treatment	Drug: VSV-GP154 Injection Drug: ATP150 Injection Drug: ATP152 Injection Drug: Ezabenlimab Infusion
No Intervention: Cohort C Observational

Outcome Measures

Primary Outcome Measures

Occurrence of dose-limiting toxicity (DLT) [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. [Throughout the study, on average 2.4 years]
Part C

Secondary Outcome Measures

Proportion of patients achieving ctDNA clearance [Up to 12 months]
Part C
Proportion of patients experiencing ctDNA non-progression [up to 12 months]
Part C
Occurrence of dose-limiting toxicity (DLT) [Throughout the study, up to 7.5 months]
Part C

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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