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

April 30, 2026 updated by: AstraZeneca

Open-label, Phase 1, Multi-Center Master Protocol to Evaluate the Safety and Preliminary Anti-Tumor Activity of TCR-engineered T Cells Recognizing KRAS Mutations in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • Research Site
      • Los Angeles, California, United States, 90095
        • Recruiting
        • Research Site
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Research Site
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • Research Site
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Research Site
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Research Site
      • New York, New York, United States, 10016
        • Recruiting
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15237
        • Recruiting
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Research Site
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Research Site
      • Galveston, Texas, United States, 77555
        • Recruiting
        • Research Site
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key 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

Key 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NT-112
Part A Dose Escalation and Part B Dose Expansion of NT-112
Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12D
NT-112 targets KRAS G12D in the context of HLA-C*08:02
Experimental: AZD0240
Part A Dose Escalation and Part B Dose Expansion of AZD0240
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Through study completion, an average of 2 years
Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Through study completion, an average of 2 years
Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE)
Time Frame: 28 days after infusion
Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
28 days after infusion
Part B (Expansion): Further evaluate the safety of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: 28 days after infusion
Incidence of DLTs, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)
28 days after infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion

Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, determined by Investigator assessment

  • Best objective response (BOR)
  • Duration of response (DOR)
  • Clinical benefit rate (CBR) (complete response [CR], partial response [PR], stable disease [SD])
  • Time to response (TTR)
  • Progression-free survival (PFS)
  • Overall survival (OS)
Up to 24 months post-infusion
Part B (Dose Expansion): Evaluate the preliminary anti-tumor activity of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post infusion

Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, determined by Investigator assessment

  • Best objective response (BOR)
  • Duration of response (DOR)
  • Clinical benefit rate (CBR) (complete response [CR], partial response [PR], stable disease [SD])
  • Time to response (TTR)
  • Progression-free survival (PFS)
  • Overall survival (OS)
Up to 24 months post infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 22, 2024

Primary Completion (Estimated)

August 30, 2027

Study Completion (Estimated)

November 18, 2043

Study Registration Dates

First Submitted

January 9, 2024

First Submitted That Met QC Criteria

January 18, 2024

First Posted (Actual)

January 23, 2024

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NT-112-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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