Master Protocol of TCR-modified T Cell Therapy Targeting HLA-restricted KRAS Antigen Administered in Adult Patients With Metastatic or Locally Advanced PDAC
ANOC-001 (TCR-T cells targeting KRAS G12V mutation presented by specific HLA alleles)ANOC-002 (TCR-T cells targeting KRAS G12V mutation presented by specific HLA alleles)ANOC-003 (TCR-T cells targeting KRAS G12D mutation presented by specific HLA alleles)
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.
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.
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
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Phase 1-Proportion of participants with dose limiting toxicity of ANOC-001, ANOC-002 and ANOC-003, graded according to American Society of Transplantation and Cellular Therapy (ASTCT) consensus criteria. — First infusion through Day 28
Phase 1-Number of participants with adverse events graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v5.0. — First infusion through Day 28
Phase 1- Identification of the Maximum tolerated dose/Maximum administered dose and Recommended Phase 2 Dose of ANOC-001/ANOC-002/ANOC-003 cells that can be administered safely in patients with metastatic and locally advanced PDAC. — First infusion through Day 28
Phase 2-Number of participants with adverse events of special interest (AESI) according to NCI CTCAE v5.0. — Baseline through 24 months post-treatment
Phase 2- Proportion of participants with Objective Response Rate (ORR) defined as the number of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST v1.1 divided by the number of treated patients. — Baseline through 24 months post-treatment
Phase 2-Proportion of participants with Clinical benefit rate (CBR) defined as percentage of patients with stable disease (SD) more than 3 months, or PR/CR from the time of study treatment. — Baseline through 24 months post-treatment
Phase 2-Proportion of participants with Clinical benefit determined by the investigator, assessed anytime at 8- to 12-week intervals post TCR-T cell infusion. — Baseline through 24 months post-treatment
Trial sites (10)
Facility
City
Region
Status
Herlev and Gentofte University Hospital
Copenhagen
Denmark
Recruiting
Charité Universitätsmedizin Berlin
Berlin
Germany
Recruiting
Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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