Actively Recruiting
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
Led by AstraZeneca · Updated on 2026-05-13
45
Participants Needed
18
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating NT-175, an autologous T cell therapy genetically engineered to target the TP53 R175H mutation in solid tumors. This Phase 1, open-label, multicenter study focuses on adults with unresectable, advanced, or metastatic non-small cell lung cancer, colorectal adenocarcinoma, head and neck squamous cell carcinoma, pancreatic adenocarcinoma, ovarian cancer, breast cancer, or other solid tumors positive for both HLA-A*02:01 and TP53 R175H mutation. The study aims to assess the safety and early anti-tumor activity of NT-175. The study includes a Dose Escalation phase to identify the maximum tolerated dose (MTD) of NT-175, followed by a Disease Histology Evaluation to determine the recommended Phase 2 dose (RP2D) and further safety. Then, a Disease Cohort Expansion phase evaluates preliminary anti-tumor activity and safety at the RP2D in specific tumor types. The treatment involves pre-conditioning with chemotherapy drugs fludarabine and cyclophosphamide, a single infusion of the engineered T cells, and post-infusion treatment with recombinant interleukin-2 (rIL-2). Participants will be monitored for safety up to 24 months after infusion, with assessments including imaging scans to measure tumor lesions. Researchers will evaluate preliminary anti-tumor activity and safety during this period. The study includes regular visits and tests to ensure participant health and treatment response. The total duration of follow-up allows long-term monitoring of safety and effectiveness signals in this patient population.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at the time of informed consent
- Capable of giving signed informed consent
- Diagnosed with one of the following histologies: NSCLC, colorectal adenocarcinoma, HNSCC, pancreatic adenocarcinoma, breast cancer, ovarian cancer, or any other solid tumor
- Tumors must have TP53 R175H mutation and be HLA-A*02:01 positive confirmed by a certified laboratory
- Advanced solid cancer defined as unresectable, advanced, and/or metastatic (Stage III or IV) after at least one approved systemic standard treatment with no curative options
- At least one measurable lesion by CT or MRI per RECIST version 1.1
- ECOG performance status of 0 to 1 at enrollment
- Adequate blood, kidney, liver, lung, and heart function
- Likely to complete study visits and comply with study requirements as judged by investigator
You will not qualify if you...
- Any other primary malignancy within 3 years prior to enrollment except non-melanoma skin cancer, carcinoma in situ, or low-grade prostate cancer
- Known active primary central nervous system malignancy
- Prior adoptive cell and gene therapy, allogeneic stem cell transplant, or solid organ transplant
- History of stroke or transient ischemic attack within 12 months prior to enrollment
- History of significant cardiac disease within 6 months prior or any prior heart failure
- Systemic therapy within at least 2 weeks or three half-lives prior to enrollment
- Severe immediate hypersensitivity to cyclophosphamide, fludarabine, or recombinant interleukin-2, or known allergy to methotrexate, gentamicin, or other aminoglycosides
- Any primary immunodeficiency
- Live vaccine within 4 weeks prior to enrollment or plans for live vaccine before treatment
- Active immune-mediated disease requiring systemic steroids or immunosuppressive therapy (except related to prior checkpoint inhibitor therapy)
- Female of childbearing potential who is lactating or breastfeeding at enrollment
- Known diagnosis or family history of Li-Fraumeni syndrome
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 28 days after infusion
Participants receive pre-conditioning chemotherapy followed by a single infusion of engineered T cells targeting TP53 R175H, and post-infusion recombinant interleukin-2 (rIL-2).
1 infusion visit and multiple follow-up visits during treatment period
Duration - Up to 24 months after infusion
Participants are monitored for safety and preliminary anti-tumor activity after treatment.
Regular visits during follow-up period
Trial Site Locations
Total: 18 locations
1
Research Site
Gilbert, Arizona, United States, 85234
Actively Recruiting
2
Research Site
Duarte, California, United States, 91010
Actively Recruiting
3
Research Site
Newport Beach, California, United States, 92663
Actively Recruiting
4
Research Site
Santa Monica, California, United States, 90404
Actively Recruiting
5
Research Site
Jacksonville, Florida, United States, 32224
Actively Recruiting
6
Research Site
Miami, Florida, United States, 33136
Withdrawn
7
Research Site
Tampa, Florida, United States, 33612
Withdrawn
8
Research Site
Boston, Massachusetts, United States, 02115
Actively Recruiting
9
Research Site
New Brunswick, New Jersey, United States, 08901
Actively Recruiting
10
Research Site
New York, New York, United States, 10065
Actively Recruiting
11
Research Site
Charlotte, North Carolina, United States, 28204
Withdrawn
12
Research Site
Winston-Salem, North Carolina, United States, 27103
Withdrawn
13
Research Site
Portland, Oregon, United States, 97213
Actively Recruiting
14
Research Site
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
15
Research Site
Nashville, Tennessee, United States, 37203
Actively Recruiting
16
Research Site
Houston, Texas, United States, 77030
Actively Recruiting
17
Research Site
Round Rock, Texas, United States, 78665
Actively Recruiting
18
Research Site
Milwaukee, Wisconsin, United States, 53226
Actively Recruiting
Research Team
A
AstraZeneca Clinical Study Information Center
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
3
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