Phase 1 Study to Investigate TCRTs KRAS Mutation in Unresectable, Advanced, and/or Metastatic Solid Tumors

NCT ID: NCT06218914

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-22

Study Completion Date

2044-04-15

Brief Summary

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Phase I Study, a master protocol to investigate TCR-Engineered T cells recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.

Detailed Description

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This is a Phase 1, open-label, Phase 1, Multi-Center Master Protocol to evaluate the safety and preliminary Anti-Tumor activity of TCR-Engineered T cells (KRAS TCRTs) recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.

Conditions

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Non-small Cell Lung Cancer Colorectal Carcinoma Pancreatic Ductal Adenocarcinoma Endometrial Cancer Solid Tumor, Adult KRAS G12D

Keywords

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TCR-T cell therapy KRAS KRAS G12D Autologous PDAC NSCLC Colorectal Cancer Solid tumors Pancreatic Ductal Adenocarcinoma HLA-C*08:02 HLA-A*11:01 HLA-A*11:02

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NT-112

Part A Dose Escalation and Part B Dose Expansion of NT-112

Group Type EXPERIMENTAL

NT-112: Autologous, engineered T Cells targeting KRAS G12D

Intervention Type BIOLOGICAL

NT-112 targets KRAS G12D in the context of HLA-C\*08:02

AZD0240

Part A Dose Escalation and Part B Dose Expansion of AZD0240

Group Type EXPERIMENTAL

AZD0240: Autologous, engineered T Cells targeting KRAS G12D

Intervention Type BIOLOGICAL

AZD0240 targets KRAS G12D in the context of HLA-A\*11:01 or HLA-A\*11:02

Interventions

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NT-112: Autologous, engineered T Cells targeting KRAS G12D

NT-112 targets KRAS G12D in the context of HLA-C\*08:02

Intervention Type BIOLOGICAL

AZD0240: Autologous, engineered T Cells targeting KRAS G12D

AZD0240 targets KRAS G12D in the context of HLA-A\*11:01 or HLA-A\*11:02

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years
* Diagnosed with NSCLC, Colorectal adenocarcinoma, Pancreatic adenocarcinoma, Endometrial Cancer or any other solid tumor
* Tumors must harbor a KRAS G12D variant mutation and subject must be HLA-C\*08:02 positive, HLA-A\*11:01 or HLA-A\*11:02 positive in at least one allele
* Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
* Presence of at least 1 measurable lesion per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment

Exclusion Criteria

* Any other primary malignancy within the 3 years prior to enrollment (except for non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or low-grade prostate cancer
* Known, active primary central nervous system (CNS) malignancy
* History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
* History of stroke or transient ischemic attack within the 12 months prior to enrollment.
* History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
* Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
* Any form of primary immunodeficiency.
* Active immune-mediated disease requiring systemic steroids or other immunosuppressive treatment (except if related to prior checkpoint inhibitor therapy)
* Female of childbearing potential who is lactating or breast feeding at the time of enrollment
* Prior treatment with pan-KRAS or KRAS G12D targeting agents unless presence of KRAS G12D mutation is confirmed after the completion of treatment with pan-KRAS or KRAS G12D targeting agents.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Duarte, California, United States

Site Status RECRUITING

Research Site

Los Angeles, California, United States

Site Status RECRUITING

Research Site

Newport Beach, California, United States

Site Status RECRUITING

Research Site

Jacksonville, Florida, United States

Site Status NOT_YET_RECRUITING

Research Site

Miami, Florida, United States

Site Status WITHDRAWN

Research Site

Chicago, Illinois, United States

Site Status RECRUITING

Research Site

Westwood, Kansas, United States

Site Status RECRUITING

Research Site

St Louis, Missouri, United States

Site Status RECRUITING

Research Site

New York, New York, United States

Site Status RECRUITING

Research Site

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Research Site

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Research Site

Nashville, Tennessee, United States

Site Status RECRUITING

Research Site

Dallas, Texas, United States

Site Status RECRUITING

Research Site

Galveston, Texas, United States

Site Status RECRUITING

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Aberdeen, Washington, United States

Site Status RECRUITING

Research Site

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

Phone: 1-877-240-9479

Email: [email protected]

Other Identifiers

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NT-112-301

Identifier Type: -

Identifier Source: org_study_id