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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 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. Who Should NOT Join This Trial: 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. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

BIOLOGICAL

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

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.

BIOLOGICAL

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

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.

BIOLOGICAL

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

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

Locations (8)

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