A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

NCT ID: NCT05877599

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-12

Study Completion Date

2029-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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 solid tumors.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a Phase 1, open-label, multicenter study to evaluate the safety and preliminary antitumor activity of NT-175 in HLA-A\*02:01 subjects with unresectable, advanced, and/or metastatic NSCLC, colorectal adenocarcinoma, HNSCC, pancreatic adenocarcinoma, ovarian cancer, breast cancer, or any other solid tumor histologies that are positive for the TP53 R175H mutation.

Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible solid tumor histologies and will evaluate the safety and MTD.

Disease Histology Evaluation will further evaluate the safety and preliminary anti-tumor activity at or below the MTD in disease specific histologies and determine the RP2D. .

Disease Cohort Expansion will further evaluate the preliminary anti-tumor activity and safety of NT-175 at the RP2D in disease specific settings.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dose Escalation and Expansion

Dose Escalation of TCR T cell product

Group Type EXPERIMENTAL

Autologous, engineered T Cells targeting TP53 R175H

Intervention Type BIOLOGICAL

* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
* Single infusion TCR T cells
* Post-infusion recombinant interleukin-2 (rIL-2)

Part 1: Disease Histology Evaluation

TCR T Cell Product at the MTD

Group Type EXPERIMENTAL

Autologous, engineered T Cells targeting TP53 R175H

Intervention Type BIOLOGICAL

* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
* Single infusion TCR T cells
* Post-infusion recombinant interleukin-2 (rIL-2)

Part 2: Disease Cohort Expansion

TCR T Cell Product at the RP2D

Group Type EXPERIMENTAL

Autologous, engineered T Cells targeting TP53 R175H

Intervention Type BIOLOGICAL

* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
* Single infusion TCR T cells
* Post-infusion recombinant interleukin-2 (rIL-2)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Autologous, engineered T Cells targeting TP53 R175H

* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
* Single infusion TCR T cells
* Post-infusion recombinant interleukin-2 (rIL-2)

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

AstraZeneca

Role: STUDY_DIRECTOR

AstraZeneca

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Research Site

Gilbert, Arizona, United States

Site Status RECRUITING

Research Site

Duarte, California, United States

Site Status RECRUITING

Research Site

Newport Beach, California, United States

Site Status RECRUITING

Research Site

Santa Monica, California, United States

Site Status RECRUITING

Research Site

Jacksonville, Florida, United States

Site Status RECRUITING

Research Site

Miami, Florida, United States

Site Status WITHDRAWN

Research Site

Tampa, Florida, United States

Site Status WITHDRAWN

Research Site

Boston, Massachusetts, United States

Site Status RECRUITING

Research Site

New Brunswick, New Jersey, United States

Site Status RECRUITING

Research Site

New York, New York, United States

Site Status RECRUITING

Research Site

Charlotte, North Carolina, United States

Site Status WITHDRAWN

Research Site

Winston-Salem, North Carolina, United States

Site Status WITHDRAWN

Research Site

Portland, Oregon, United States

Site Status RECRUITING

Research Site

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Research Site

Nashville, Tennessee, United States

Site Status RECRUITING

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Round Rock, Texas, United States

Site Status RECRUITING

Research Site

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NT-175-201

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

An Early Phase Trial of RPTR-1-201 in Advanced Solid Tumors
NCT07293754 NOT_YET_RECRUITING PHASE1/PHASE2
A Study of TIL in Advanced Solid Tumors (CZ)
NCT07294872 NOT_YET_RECRUITING PHASE1