Engineered T cells targeting KRAS mutations for advanced pancreatic cancer

Phase 1/2 Master Protocol for Open-Label, Multi-Centre, Single-Arm Sub-Studies, First in Human Clinical Studies of TCR-T Therapy (Autologous TCR- Modified T-Cell Therapy) Targeting Mutated Kirsten Rat Sarcoma (mutKRAS) Administered in Metastatic or Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC) Adult Patients With Specific mutKRAS and Human Leukocyte Antigen (HLA) Genotypes

This trial tests engineered T cells designed to target specific KRAS mutations in adults with metastatic or locally advanced pancreatic ductal adenocarcinoma who have received standard first-line therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Anocca AB (Government)
• Drugs / interventions: cyclophosphamide
• Locations: 8 sites (Copenhagen and 7 other locations)
• Trial ID: NCT07145450 on ClinicalTrials.gov

What this trial studies

This open-label, multi-center, single-arm Phase 1/2 program uses autologous TCR‑modified T cells engineered to recognize KRAS G12V or G12D peptides presented by specific HLA alleles. Treatment involves leukapheresis to collect immune cells, ex vivo TCR modification and expansion, lymphodepletion, and infusion of the TCR‑T product with follow-up for safety, cell expansion/persistence and anti-tumor activity. Each sub-study uses a classical 3+3 dose-escalation to identify a tolerable dose, followed by Phase 2 expansion at the selected dose. The trial is enrolling adults with metastatic or locally advanced PDAC whose tumors harbor the target KRAS mutation and required HLA type.

Who should consider this trial

Good fit: Ideal candidates are adults with metastatic or locally advanced PDAC, confirmed KRAS G12V or G12D mutation and the required HLA allele, who have derived clinical benefit from first-line standard therapy and can undergo leukapheresis and lymphodepletion.

Not a fit: Patients without the relevant KRAS mutation or the matching HLA alleles, those with rapidly progressive disease after first-line therapy, or those medically unfit for leukapheresis or lymphodepleting chemotherapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could shrink tumors that carry the target KRAS mutations and provide a new, mutation-specific immunotherapy option for a subset of patients with advanced pancreatic cancer.

How similar studies have performed: HLA-restricted, mutation-targeting TCR‑T approaches are experimental; small early trials and case reports have reported occasional responses but broad, reproducible success in pancreatic cancer has not yet been demonstrated.

Eligibility criteria

Inclusion Criteria:

1. Adult patient (18 years or older) with newly diagnosed metastatic PDAC or locally advance PDAC disease.
2. HLA genotyping confirmed with a high-resolution method.
3. Confirmed KRAS G12V or KRAS G12D mutation in tumour using biopsy sample.
4. Fertile male and female patients must use a highly effective contraceptive method before, during, and for at least 6 months after the last mutKRAS TCR infusion. Acceptable contraception for women includes implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence, or a partner who has been vasectomized for at least 6 months. Acceptable contraception for male includes having had a vasectomy for at least 6 months, sexual abstinence, to condoms plus spermicide. Fertile female and male patients must adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide (refer to SmPC).
5. Confirmed clinical benefit to SoC treatments and absence of disease progression according to the PI judgement.
6. Measurable disease by RECIST 1.1 criteria at the time of first treatment. Baseline imaging (for example, diagnostic CT chest/abdomen/pelvis and imaging of the affected extremity or brain, as appropriate), magnetic resonance imaging (MRI or CT scan) must be obtained within 8 weeks of the first planned T cell infusion. CT can be substituted for MRI in patients unable to have CT contrast.

Exclusion Criteria:

1. Another malignancy other than PDAC.
2. Current or history of brain metastasis.
3. Patient with known genetic status for whom other treatments are available e.g. BRCA, MSI-H.

Where this trial is running

Copenhagen and 7 other locations

• Herlev and Gentofte University Hospital — Copenhagen, Denmark (Active_not_recruiting)
• Charité Universitätsmedizin Berlin — Berlin, Germany (Active_not_recruiting)
• Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus — Dresden, Germany (Recruiting)
• Universitaetsklinikum Heidelberg — Heidelberg, Germany (Active_not_recruiting)
• University Hospital and Faculty of Medicine Eberhard Karls University Tübingen — Tübingen, Germany (Active_not_recruiting)
• Amsterdam UMC - VU Medical Center — Amsterdam, Netherlands (Active_not_recruiting)
• Radboud University Medical Center — Nijmegen, Netherlands (Active_not_recruiting)
• Karolinska University Hospital — Stockholm, Sweden (Recruiting)

Study contacts

• Study coordinator: Sheila Forsman

Conditions PDAC