Overview
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.
Description
This is a phase 1/2 study of engineered autologous T cells (TCR targeting KRAS G12V (ANOC-001 sub-study 1), (ANOC-002 sub-study 2) and KRAS 12D (ANOC-003 sub-study 3) capable of recognizing the tumour antigen(s), activating the T cells and exerting anti-tumour activity in patients with metastatic or locally advanced PDAC following a SoC first-line therapy.
The protocol procedures will be performed in two parts. Part 1 includes prescreening /screening eligibility, enrolment and leukapheresis. Part 2 includes lymphodepletion, TCR-T cell infusion and all study assessments until the end-of-treatment or early discontinuation .
In the dose escalation part of each sub-study, two doses will be assessed in a classical 3+3 dose escalation design to assess the safety and tolerability of TCR-T cells with the goal to identify the optimal safe dose for each product.
Eligibility
Inclusion Criteria:
- Adult patient (18 years or older) with newly diagnosed metastatic PDAC or locally advance PDAC disease.
- HLA genotyping confirmed with a high-resolution method.
- Confirmed KRAS G12V or KRAS G12D mutation in tumour using biopsy sample.
- 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).
- Confirmed clinical benefit to SoC treatments and absence of disease progression according to the PI judgement.
- 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:
- Another malignancy other than PDAC.
- Current or history of brain metastasis.
- Patient with known genetic status for whom other treatments are available e.g. BRCA, MSI-H.