NCT07145450

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: Anocca AB · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 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.

Conditions

• PDAC

Interventions

Type	Name	Description
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

Timeline

• Start date: 2025-07-03
• Primary completion: 2030-04-02
• Completion: 2030-07-31
• First posted: 2025-08-28
• Last updated: 2025-08-28

Locations

8 sites across 4 countries: Denmark, Germany, Netherlands, Sweden