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.
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 pre- screening/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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
96
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.
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.
Herlev and Gentofte University Hospital
Copenhagen, Denmark
ACTIVE_NOT_RECRUITINGCharité Universitätsmedizin Berlin
Berlin, Germany
ACTIVE_NOT_RECRUITINGTechnische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus
Dresden, Germany
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.
Time frame: 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.
Time frame: 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.
Time frame: First infusion through Day 28
Phase 2-Number of participants with adverse events of special interest (AESI) according to NCI CTCAE v5.0.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through 24 months post-treatment
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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
Universitaetsklinikum Heidelberg
Heidelberg, Germany
ACTIVE_NOT_RECRUITINGUniversity Hospital and Faculty of Medicine Eberhard Karls University Tübingen
Tübingen, Germany
ACTIVE_NOT_RECRUITINGAmsterdam UMC - VU Medical Center
Amsterdam, Netherlands
ACTIVE_NOT_RECRUITINGRadboud University Medical Center
Nijmegen, Netherlands
ACTIVE_NOT_RECRUITINGKarolinska University Hospital
Stockholm, Sweden
RECRUITINGPhase 1 and Phase 2: Percentage of patients who receive protocol-defined target dose of ANOC-001, ANOC-002 and ANOC-003.
Time frame: From leukapheresis through product release and infusion (Day 1), on an average of 2-4 months for each participant
Phase 1 and Phase 2: Proportion of investigational product- ANOC-001, ANOC-002 and ANOC-003 that comply with the specifications as compared to the total number of the IMP manufactured
Time frame: From leukapheresis through product release and infusion (Day 1), on an average of 2-4 months for each participant
Phase 1 and Phase 2-Maximum expansion and persistence of TCR T cells following infusion by quantitative PCR
Time frame: Baseline through 24 months post-treatment
Phase 1 and Phase 2- Proportion of participants achieving Progression Free Survival (PFS) defined as the time from study treatment to the first occurrence of disease progression or death, whichever occurs first.
Time frame: Baseline through 24 months post-treatment
Phase 1 and Phase 2- Proportion of participants achieving Overall Survival (OS) defined as the time from study treatment to death from any cause.
Time frame: Baseline through 24 months post-treatment
Phase 1 and Phase 2- Proportion of participants achieving Duration of Response (DoR) defined as the time from study treatment to disease progression or death in patients who achieve CR or PR.
Time frame: Baseline through 24 months post-treatment