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

NCT07145450 | Recruiting Phase 1 DMC

• 1 other identifier: CTP-ANOC-IS-001
• Study Type: interventional
• Target: 96
• Locations: 4 countries
• Sites: 8

Brief 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.

Conditions

PDAC

Outcome Measures

Primary Outcomes (7)

• 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

Secondary Outcomes (6)

• Phase 1 and Phase 2: Percentage of patients who receive protocol-defined target dose of ANOC-001, ANOC-002 and ANOC-003.

  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

  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

  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.

  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.

  Baseline through 24 months post-treatment

Other Outcomes (6)

• Exploratory-Phase 1 and 2-To evaluate correlation of T cell persistence with safety and clinical response and with phenotype of infused T cells

  Baseline through 24 months post-treatment

• Exploratory-Phase 1 and 2-To evaluate types and levels of cytokines in peripheral blood

  Baseline through 24 months post-treatment

• Exploratory-Phase 1 and 2-To evaluate change in ctDNA and CTC/exosome load

  Baseline through 24 months post-treatment

Study Arms (3)

ANOC-001

OTHER

Treatment

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

ANOC-002

OTHER

Treatment

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

ANOC-003

OTHER

Treatment

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

Interventions

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

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-001

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

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

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anocca AB: lead

Study Sites (8)

Herlev and Gentofte University Hospital

Copenhagen, Denmark

ACTIVE NOT RECRUITING

Charité Universitätsmedizin Berlin

Berlin, Germany

ACTIVE NOT RECRUITING

Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus

Dresden, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, Germany

ACTIVE NOT RECRUITING

University Hospital and Faculty of Medicine Eberhard Karls University Tübingen

Tübingen, Germany

ACTIVE NOT RECRUITING

Amsterdam UMC - VU Medical Center

Amsterdam, Netherlands

ACTIVE NOT RECRUITING

Radboud University Medical Center

Nijmegen, Netherlands

ACTIVE NOT RECRUITING

Karolinska University Hospital

Stockholm, Sweden

RECRUITING

Central Study Contacts

Sheila Forsman

CONTACT

+46708414725; sheila.forsman@anocca.com

Anocca AB

CONTACT

+46841080701; clinical.trials@anocca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: August 28, 2025
• Study Start: July 3, 2025
• Primary Completion (Estimated): April 2, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); DK (1); DE (4); SE (1)