Clinical trial NCT05846516: A Study to Evaluate ATP150/ATP152, VSV-GP154 and Ezabenlimab in Patients With KRAS G12D/G12V Mutated PDAC (KISIMA-02)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Ductal Adenocarcinoma
Keywords: KISIMA-02
PDAC
ATP150
ATP152
Ezabenlimab
VSV-GP154
Adjuvant setting
Resected pancreatic ductal adenocarcinoma
Metastatic pancreatic ductal adenocarcinoma
Locally advanced pancreatic ductal adenocarcinoma
Resected PDAC
Metastatic PDAC
LAPC
Lead sponsor: Amal Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Boehringer Ingelheim
First posted: 2023-05-06
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: For Part C: parallel and randomized
Primary purpose: TREATMENT

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:

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: 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: dose escalation

NOT STARTED YET - Part C (resected PDAC patients) Cohort C: ATP150/ATP152, Ezabenlimab and VSV-GP154 treatment (treatment versus observational arm)

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of dose-limiting toxicity (DLT)
timeFrame: Over at least 35 days
measure: Disease-free survival (DFS), defined as the time from randomization until confirmed relapse or death from any cause, whichever occurs earlier.
timeFrame: Throughout the study, on average 2.4 years
Secondary outcomes:
measure: Proportion of patients achieving ctDNA clearance
timeFrame: Up to 12 months
measure: Proportion of patients experiencing ctDNA non-progression
timeFrame: up to 12 months
measure: Occurrence of dose-limiting toxicity (DLT)
timeFrame: Throughout the study, up to 7.5 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START - South Texas Accelerated Research Therapeutics
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Lausanne
country: Switzerland
facility: University Hospital of Lausanne (CHUV)
state: Default
city: Bern
country: Switzerland
facility: University Hospital of Bern (Inselspital)
city: Geneva
country: Switzerland
facility: University Hospitals of Geneva (HUG)
Study officials:
affiliation: NYU Langone Health
name: Paul Oberstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Shubham Pant, MD
role: PRINCIPAL_INVESTIGATOR
References: