T cell therapy targeting KRAS G12D in advanced solid tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Research Site
  Duarte, California, United States Recruiting
• Research Site
  Los Angeles, California, United States Recruiting
• Research Site
  Newport Beach, California, United States Recruiting
• Research Site
  Jacksonville, Florida, United States Recruiting
• Research Site
  Chicago, Illinois, United States Recruiting
• Research Site
  Westwood, Kansas, United States Recruiting

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• VS-7375 for adults with KRAS G12D-mutated advanced solid tumors.

  This trial tests VS-7375, alone and combined with other cancer drugs, in adults with unresectable or metastatic solid tumors that have the KRAS G12D mutation.

  Recruiting at 22 sites Phase 1/2 Verastem, Inc. · Los Angeles, California and 21 other locations · NCT07020221

• DR-0202 for advanced, relapsed, or treatment-resistant carcinomas

  This trial tests DR-0202 in adults with advanced or metastatic carcinomas—such as certain breast, lung, cervical, and prostate cancers—that have relapsed or stopped responding to standard treatments.

  Recruiting at 10 sites Phase 1 Dren Bio · Denver, Colorado and 9 other locations · NCT06999187

• BBO-11818 treatment for adults with KRAS mutant cancer

  This study is testing a new drug called BBO-11818 to see if it can help adults with certain types of cancer that have specific KRAS mutations.

  Recruiting at 17 sites Phase 1 TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) · Los Angeles, California and 16 other locations · NCT06917079

• Evaluating BDTX-4933 for patients with specific cancer mutations

  This study is testing a new drug called BDTX-4933 to see if it can help adults with advanced cancers that have certain gene mutations feel better and improve their treatment options.

  Recruiting at 34 sites Phase 1/2 Servier · Gilbert, Arizona and 48 other locations · NCT05786924

• ABBV-253 in adults with advanced solid tumors

  This study tests ABBV-253 to see if it is safe, how it affects the cancer, and how the drug moves in the body for adults with advanced solid tumors.

  Recruiting at 3 sites Phase 1 AbbVie · Grand Rapids, Michigan and 2 other locations · NCT07807956

• First-in-human STRO-006 in adults with certain recurrent or metastatic solid tumors

  This study tests STRO-006 alone and with pembrolizumab in adults with certain head and neck, lung, esophageal, gastric, colorectal cancers to see if it is safe and shows early anticancer activity.

  Recruiting at 3 sites Phase 1 Sutro Biopharma, Inc. · Orlando, Florida and 5 other locations · NCT07807345

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.