Home › Trials › NCT06218914

T cell therapy targeting KRAS G12D in advanced solid tumors

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 1 Interventional AstraZeneca · NCT06218914

This trial will test whether autologous T cells engineered to recognize KRAS G12D can help adults with unresectable or metastatic solid tumors who have the matching HLA type.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment108 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Locations18 sites (Duarte, California and 17 other locations)
Trial IDNCT06218914 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label, multi-center master protocol testing autologous TCR-engineered T cells (KRAS TCR-Ts) that target the KRAS G12D mutation. Eligible adults must have an unresectable, advanced, or metastatic solid tumor with a KRAS G12D variant and be positive for HLA-C*08:02 or HLA-A*11:01/11:02, have ECOG 0–1, measurable disease by RECIST v1.1, and prior standard systemic therapy. Subjects undergo leukapheresis to produce personalized T cells (NT-112 or AZD0240) which are then infused and followed for safety and preliminary anti-tumor activity. The primary focus is safety and tolerability with secondary signals of tumor response monitored at participating California clinical sites.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with unresectable or metastatic solid tumors that harbor the KRAS G12D mutation, who are HLA-C*08:02 or HLA-A*11:01/11:02 positive, have ECOG performance status 0–1, measurable disease, and have received at least one prior line of standard systemic therapy.

Not a fit: Patients without the KRAS G12D mutation or the required HLA types, those with poor performance status, active untreated CNS disease, or recent other malignancies are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could produce meaningful tumor responses in patients with KRAS G12D-positive advanced cancers who have exhausted standard treatment options.

How similar studies have performed: This HLA-restricted, KRAS-targeted TCR-T approach is novel with limited early clinical reports and case-level signals of activity but has not yet been broadly proven in larger trials.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Duarte, California and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-small Cell Lung CancerColorectal CarcinomaPancreatic Ductal AdenocarcinomaEndometrial CancerSolid Tumor, AdultKRAS G12DTCR-T cell therapyKRAS
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.