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

Pancreatic Ductal Adenocarcinoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05846516
• Other study ID #: KISIMA-02
• Status: Recruiting
• Phase: Phase 1
• Start date: March 13, 2023
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: Amal Therapeutics
• Contact: AMAL Therapeutics
• Phone: +41 (0) 22 594 39 52
• Email: RESContact.GVA[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: March 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• VSV-GP154
Injection
• ATP150
Injection
• ATP152
Injection
• Ezabenlimab
Infusion

Locations

Country	Name	City	State
Switzerland	University Hospital of Bern (Inselspital)	Bern
Switzerland	University Hospitals of Geneva (HUG)	Geneva
Switzerland	University Hospital of Lausanne (CHUV)	Lausanne	Default
United States	University of Colorado Hospital	Aurora	Colorado
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	University of Florida	Gainesville	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California Los Angeles (UCLA)	Los Angeles	California
United States	USC/Norris Comprehensive Center	Los Angeles	California
United States	NYU Langone Health	New York	New York
United States	START - South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Amal Therapeutics	Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of dose-limiting toxicity (DLT)	Part A and B	Over at least 35 days
Primary	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	Proportion of patients achieving ctDNA clearance	Part C	Up to 12 months
Secondary	Proportion of patients experiencing ctDNA non-progression	Part C	up to 12 months
Secondary	Occurrence of dose-limiting toxicity (DLT)	Part C	Throughout the study, up to 7.5 months