Recruiting
Phase 1

NT-175

Sponsor:

AstraZeneca

Code:

NCT05877599

Conditions

Non-small Cell Lung Cancer

Head and Neck Squamous Cell Carcinoma

Colorectal Carcinoma

Pancreatic Adenocarcinoma

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

NT-175

Study Details

Brief summary:

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A\*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies

Conditions

Non-small Cell Lung Cancer

Head and Neck Squamous Cell Carcinoma

Colorectal Carcinoma

Pancreatic Adenocarcinoma

Breast Cancer

Study ID

NCT05877599

Start date

Jul 12, 2023

Status verified date

Aug, 2026

Completion date

Jul 31, 2029

Anticipated

Primary completion date

Jul 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria (Module 1)

  • Subjects must be at least 18 years of age
  • 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)
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Adequate hematological, renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria (Module 1)

  • Any another primary malignancy within the 3 years prior to enrollment
  • 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 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.
  • Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Key Inclusion Criteria (Module 2 - hematological malignancies)

  • At least 18 years of age
  • Diagnosis of AML or MDS that allows for efficacy assessments
  • Confirmation of TP53 R175H variant mutation in cancer cells
  • Subject must be HLA-A\*02:01 positive (at least 1 allele)
  • ECOG performance status of 0 to 1

Key Exclusion Criteria (Module 2 - hematological malignancy)

  • Acute promyelocytic leukaemia or isolated extramedullary disease
  • Another primary malignancy within 2 years (with exceptions)
  • HSCT within 100 days or immunosuppression for GvHD within 4 weeks
  • History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells
  • Prior stroke, ischemic attack, significant cardiac disease, heart failure
  • Prior adoptive modified cell therapy
  • Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Study Design

Enrollment

45 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: NT-175 for advanced malignancies

TCR T cell therapy product

Interventions

NT-175

  • Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
  • Single infusion Autologous, engineered T Cells targeting TP53 R175H
  • Post-infusion recombinant interleukin-2 (rIL-2)

Primary outcome measure

  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours [ Time Frame: 28 days after infusion ]
  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours [ Time Frame: Up to 24 months post-infusion ]
  • Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours [ Time Frame: Up to 24 months after infusion ]
  • Module 2: Safety of NT-175 in participants with haematological malignancies [ Time Frame: Up to 28 days after infusion ]
  • Module 2: Safety of NT-175 in participants with haematological malignancies [ Time Frame: Up to 24 months after infusion ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

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

Locations

Research Site

Recruiting

Gilbert, Arizona, United States, 85234

Research Site

Recruiting

Duarte, California, United States, 91010

Research Site

Recruiting

Newport Beach, California, United States, 92663

Research Site

Recruiting

Santa Monica, California, United States, 90404

Research Site

Recruiting

Jacksonville, Florida, United States, 32224

Research Site

Recruiting

Boston, Massachusetts, United States, 02115

Research Site

Recruiting

New Brunswick, New Jersey, United States, 08901

Research Site

Recruiting

New York, New York, United States, 10065

Research Site

Recruiting

Portland, Oregon, United States, 97213

Research Site

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Research Site

Recruiting

Nashville, Tennessee, United States, 37203

Research Site

Recruiting

Houston, Texas, United States, 77030

Research Site

Recruiting

Round Rock, Texas, United States, 78665

Research Site

Recruiting

Milwaukee, Wisconsin, United States, 53226

More Information

Sponsor

AstraZeneca

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Keywords

  • Cell therapy
  • TP53
  • Solid tumors
  • Non-small cell lung cancer
  • Head and neck squamous cell carcinoma
  • Colorectal carcinoma
  • Pancreatic adenocarcinoma
  • Breast Cancer
  • Ovarian Cancer
  • AML
  • MDS
  • TCR

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 2026-09-01.