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Recruiting NCT06218914

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

Phase I Interventional Non-small Cell Lung Cancer Colorectal Carcinoma Pancreatic Ductal Adenocarcinoma Endometrial Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: NT-112: Autologous, engineered T Cells targeting KRAS G12D, AZD0240: Autologous, engineered T Cells targeting KRAS G12D.
Who it may be relevant to
Registry conditions: Non-small Cell Lung Cancer, Colorectal Carcinoma, Pancreatic Ductal Adenocarcinoma, Endometrial Cancer. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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

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.

Interventions

  • Biological NT-112: Autologous, engineered T Cells targeting KRAS G12D
    NT-112 targets KRAS G12D in the context of HLA-C\*08:02
  • 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

Primary outcome measures

  • 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]
  • Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE) [Time frame: 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]
Secondary outcome measures (2)
  • 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]
  • 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 18 centers
  • Research Site — Duarte
  • Research Site — Los Angeles
  • Research Site — Newport Beach
  • Research Site — Jacksonville
  • Research Site — Chicago
  • Research Site — Westwood
  • Research Site — Boston
  • Research Site — St Louis
  • … and 10 more centers

Identifiers

NCT: NCT06218914 · NT-112-301

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗