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

Amal Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Pancreatic Ductal Adenocarcinoma

Treatments: Drug: ATP150; Drug: Ezabenlimab; Drug: VSV-GP154; Drug: ATP152

Study type: Interventional

Funder types: Industry

Identifiers

NCT05846516

KISIMA-02

Details and patient eligibility

About

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.

Full 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)

Enrollment: 85 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

85 participants in 4 patient groups

Cohort A

Experimental group

Treatment:

Drug: ATP152

Drug: VSV-GP154

Drug: ATP150

Cohort B

Experimental group

Treatment:

Drug: ATP152

Drug: VSV-GP154

Drug: Ezabenlimab

Drug: ATP150

Cohort C Treatment

Experimental group

Treatment:

Drug: ATP152

Drug: VSV-GP154

Drug: Ezabenlimab

Drug: ATP150

Cohort C Observational

No Intervention group