Recruiting
Phase 1

TCR-Engineered T Cells

Sponsor:

AstraZeneca

Code:

NCT06218914

Conditions

Non-small Cell Lung Cancer

Colorectal Carcinoma

Pancreatic Ductal Adenocarcinoma

Endometrial Cancer

Solid Tumor, Adult

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

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

AZD0240: Autologous, engineered T Cells targeting KRAS G12D

Study Details

Brief summary:

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.

Conditions

Non-small Cell Lung Cancer

Colorectal Carcinoma

Pancreatic Ductal Adenocarcinoma

Endometrial Cancer

Solid Tumor, Adult

Study ID

NCT06218914

Start date

Mar 22, 2024

Status verified date

Aug, 2026

Completion date

Nov 18, 2043

Anticipated

Primary completion date

Aug 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

108 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: NT-112

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

experimental: AZD0240

Part A Dose Escalation and Part B Dose Expansion of AZD0240

Interventions

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

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

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 measure

  • 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 ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Duarte, California, United States, 91010

Research Site

Recruiting

Los Angeles, California, United States, 90095

Research Site

Recruiting

Newport Beach, California, United States, 92663

Research Site

Recruiting

Jacksonville, Florida, United States, 32224

Research Site

Recruiting

Chicago, Illinois, United States, 60637

Research Site

Recruiting

Westwood, Kansas, United States, 66205

Research Site

Recruiting

Boston, Massachusetts, United States, 02115

Research Site

Recruiting

St Louis, Missouri, United States, 63110

Research Site

Recruiting

New York, New York, United States, 10016

Research Site

Recruiting

New York, New York, United States, 10065

Research Site

Recruiting

Portland, Oregon, United States, 97213

Research Site

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Research Site

Recruiting

Pittsburgh, Pennsylvania, United States, 15237

Research Site

Recruiting

Nashville, Tennessee, United States, 37203

Research Site

Recruiting

Dallas, Texas, United States, 75246

Research Site

Recruiting

Galveston, Texas, United States, 77555

Research Site

Recruiting

Houston, Texas, United States, 77030

Research Site

Recruiting

Milwaukee, Wisconsin, United States, 53226

More Information

Sponsor

AstraZeneca

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Keywords

  • 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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-08-24.