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

Study Overview

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

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.

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.

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

BIOLOGICAL: Autologous, engineered T Cells targeting TP53 R175H

NT-175-201

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-05-17	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-02-19
First Submitted that Met QC Criteria 2023-05-17	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-02-20
First Posted (ACTUAL) 2023-05-26	Results First Posted N/A	Last Verified 2025-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose Escalation and Expansion Dose Escalation of TCR T cell product	BIOLOGICAL: 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)
EXPERIMENTAL: Part 1: Disease Histology Evaluation TCR T Cell Product at the MTD	BIOLOGICAL: 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)
EXPERIMENTAL: Part 2: Disease Cohort Expansion TCR T Cell Product at the RP2D	BIOLOGICAL: 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)

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Dose Escalation and Expansion

Dose Escalation of TCR T cell product

BIOLOGICAL: 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)

EXPERIMENTAL: Part 1: Disease Histology Evaluation

TCR T Cell Product at the MTD

BIOLOGICAL: 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)

EXPERIMENTAL: Part 2: Disease Cohort Expansion

TCR T Cell Product at the RP2D

BIOLOGICAL: 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)

Primary Outcome Measures	Measure Description	Time Frame
Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175	28 days after infusion
Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Incidence of adverse events and serious adverse events	Up to 24 months post-infusion
Part 2: Further Evaluate the safety of NT-175 at the RP2D in subjects with unresectable, advanced, and/or metastatic solid tumors	Treatment-emergent adverse events, and serios adverse events	Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion

Secondary Outcome Measures	Measure Description	Time Frame
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: AstraZeneca Clinical Study Information Center

Phone Number: 1-877-240-9479

Email: information.center@astrazeneca.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: AstraZeneca, AstraZeneca

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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