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Treatment with engineered T cells for advanced solid tumors with a specific mutation

An Open-label, Phase 1, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor Activity of NT-175 in Human Leukocyte Antigen-A*02:01-Positive Adult Subjects With Unresectable, Advanced and/or Metastatic Solid Tumors That Are Positive for the TP53 R175H Mutation

PHASE1 · AstraZeneca · NCT05877599

This study is testing a new T cell therapy for patients with advanced solid tumors that have a specific mutation to see if it can help fight their cancer.

Quick facts

PhasePHASE1
Study typeInterventional
Enrollment45 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionschemotherapy, methotrexate, cyclophosphamide, fludarabine
Locations18 sites (Gilbert, Arizona and 17 other locations)
Trial IDNCT05877599 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label, multicenter study evaluates the safety and preliminary antitumor activity of NT-175, an autologous T cell therapy targeting the TP53 R175H mutation in patients with unresectable, advanced, and/or metastatic solid tumors. Eligible participants must be HLA-A*02:01 positive and have specific cancer types, including non-small cell lung cancer and breast cancer, among others. The study will involve dose escalation to determine the maximum tolerated dose (MTD) and further assess the therapy's effectiveness in specific disease cohorts.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable, advanced solid tumors harboring the TP53 R175H mutation and who are HLA-A*02:01 positive.

Not a fit: Patients without the TP53 R175H mutation or those who are not HLA-A*02:01 positive will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with advanced solid tumors that currently have limited treatment options.

How similar studies have performed: While this approach is novel in targeting the TP53 R175H mutation specifically, similar T cell therapies have shown promise in treating other solid tumors.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria

* Subjects must be at least 18 years of age, at the time of signing the informed consent.
* Subjects must be capable of giving signed informed consent.
* Subject must be diagnosed with one of the histologies below:

  * NSCLC
  * Colorectal adenocarcinoma
  * HNSCC
  * Pancreatic adenocarcinoma
  * Breast cancer
  * Ovarian cancer
  * Any other solid tumor
* Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A\*02:01 positive (at least 1 allele) as confirmed by an CLIA-accredited laboratory-based test.
* 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.
* Subject has at least 1 measurable lesion per computed tomography (CT) scan or magnetic resonance imaging (MRI) per RECIST version 1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
* Adequate hematological, renal, hepatic, pulmonary, and cardiac function
* Per Investigator judgement, subject is likely to complete study visits and/or procedures per the protocol and comply with study requirements for study participation

Key Exclusion Criteria

* Any another 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.
* History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or rIL-2; or known sensitivity or allergy to methotrexate, gentamicin, or other aminoglycosides.
* Any form of primary immunodeficiency.
* Live vaccine ≤ 4 weeks prior to enrollment or plans to have a live vaccine prior to planned lymphodepleting chemotherapy and/or NT-175 treatment.
* 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.
* Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Where this trial is running

Gilbert, Arizona 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 →

Conditions: Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Carcinoma, Pancreatic Adenocarcinoma, Breast Cancer, Other Solid Tumors, Ovarian Cancer, Cell therapy

Last reviewed 2026-05-15 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.