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

NCT05877599 | Recruiting Phase 1 FDA Drug

• 1 other identifier: NT-175-201
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 18

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 solid tumors.

Conditions

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

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; TCR

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (6)

• Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors

  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

  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

  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

  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

  Up to 24 months after infusion

Study Arms (3)

Dose Escalation and Expansion

EXPERIMENTAL

Dose Escalation of TCR T cell product

Biological: Autologous, engineered T Cells targeting TP53 R175H

Part 1: Disease Histology Evaluation

EXPERIMENTAL

TCR T Cell Product at the MTD

Biological: Autologous, engineered T Cells targeting TP53 R175H

Part 2: Disease Cohort Expansion

EXPERIMENTAL

TCR T Cell Product at the RP2D

Biological: Autologous, engineered T Cells targeting TP53 R175H

Interventions

Autologous, engineered T Cells targeting TP53 R175H BIOLOGICAL

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

Dose Escalation and Expansion; Part 1: Disease Histology Evaluation; Part 2: Disease Cohort Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (18)

Research Site

Gilbert, Arizona, 85234, United States

RECRUITING

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Newport Beach, California, 92663, United States

RECRUITING

Research Site

Santa Monica, California, 90404, United States

RECRUITING

Research Site

Jacksonville, Florida, 32224, United States

RECRUITING

Research Site

Miami, Florida, 33136, United States

WITHDRAWN

Research Site

Tampa, Florida, 33612, United States

WITHDRAWN

Research Site

Boston, Massachusetts, 02115, United States

RECRUITING

Research Site

New Brunswick, New Jersey, 08901, United States

RECRUITING

Research Site

New York, New York, 10065, United States

RECRUITING

Research Site

Charlotte, North Carolina, 28204, United States

WITHDRAWN

Research Site

Winston-Salem, North Carolina, 27103, United States

WITHDRAWN

Research Site

Portland, Oregon, 97213, United States

RECRUITING

Research Site

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Research Site

Nashville, Tennessee, 37203, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

Round Rock, Texas, 78665, United States

RECRUITING

Research Site

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Breast Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• AstraZeneca

  AstraZeneca

  STUDY DIRECTOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 26, 2023
• Study Start: July 12, 2023
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (18)