Master Protocol of TCR-modified T Cell Therapy Targeting HLA-restricted KRAS Antigen Administered in Adult Patients With Metastatic or Locally Advanced PDAC

Summary

This is an open-label, multi-centre, single-arm Phase 1/2 clinical trial of the safety, expansion, persistence and clinical activity of a set of engineered autologous T cells products each capable of recognizing a specific combination mutated KRAS and HLA, activating the T cells and exerting anti- tumour activity in patients with metastatic or locally advanced PDAC.

Interventions

• ANOC-001 (TCR-T cells targeting KRAS G12V mutation presented by specific HLA alleles) · BIOLOGICAL

  The cells will be gene edited and administered by a single IV infusion on Day 1. Drugs: Cyclophosphamide and Fludarabine will be used as a lymphodepleting chemotherapy.

• ANOC-002 (TCR-T cells targeting KRAS G12V mutation presented by specific HLA alleles) · BIOLOGICAL

  The cells will be gene edited and administered by a single IV infusion on Day 1. Drugs: Cyclophosphamide and Fludarabine will be used as a lymphodepleting chemotherapy.

• ANOC-003 (TCR-T cells targeting KRAS G12D mutation presented by specific HLA alleles) · BIOLOGICAL

  The cells will be gene edited and administered by a single IV infusion on Day 1. Drugs: Cyclophosphamide and Fludarabine will be used as a lymphodepleting chemotherapy

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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 of chest/abdomen/pelvis and imaging of the affected extremity or brain, as appropriate), or magnetic resonance imaging (MRI) 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.

Sites (10)

• Herlev and Gentofte University Hospital, Copenhagen, Denmark · RECRUITING
• Charité Universitätsmedizin Berlin, Berlin, Germany · RECRUITING
• Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus, Dresden, Germany · RECRUITING
• Universitaetsklinikum Heidelberg, Heidelberg, Germany · RECRUITING
• Universitaetsklinikum Leipzig - Universitaeren Krebszentrum (UCCL), Leipzig, Germany · NOT_YET_RECRUITING
• Ludwig-Maximilians-Universitaet Muenchen (LMU) Klinikum der Universitaet Muenchen - Campus Grosshadern - Medizinische Klinik und Poliklinik III, München, Germany · NOT_YET_RECRUITING
• University Hospital and Faculty of Medicine Eberhard Karls University Tübingen, Tübingen, Germany · RECRUITING
• Amsterdam UMC - VU Medical Center, Amsterdam, Netherlands · RECRUITING
• Radboud University Medical Center, Nijmegen, Netherlands · RECRUITING
• Karolinska University Hospital, Stockholm, Sweden · RECRUITING