NCT05877599

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

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1 nonsmall-cell-lung-cancer

Timeline
37mo left

Started Jul 2023

Longer than P75 for phase_1 nonsmall-cell-lung-cancer

Geographic Reach
1 country

18 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress51%
Jul 2023Jul 2029

First Submitted

Initial submission to the registry

May 17, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

May 26, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

July 12, 2023

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2029

Last Updated

July 13, 2026

Status Verified

July 1, 2026

Enrollment Period

6.1 years

First QC Date

May 17, 2023

Last Update Submit

July 10, 2026

Conditions

Pancreatic AdenocarcinomaBreast CancerOther Solid TumorsOvarian CancerColorectal CarcinomaNon-small Cell Lung CancerHead and Neck Squamous Cell CarcinomaMyeloid Neoplasms (AML/MDS)

Keywords

Cell therapyTP53Solid tumorsNon-small cell lung cancerHead and neck squamous cell carcinomaColorectal carcinomaPancreatic adenocarcinomaBreast CancerOvarian CancerAMLMDSTCR

Outcome Measures

Primary Outcomes (5)

  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours

    Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175

    28 days after infusion

  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours

    Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)

    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

    Per RECIST v1.1 determined by Investigator assessment: * Objective Response Rate (ORR) * Best Overall Response (BOR) * Duration of Response (DOR) * Clinical Benefit Rate (CBR) * Time to Response (TTR) * Progression-free survival (PFS) * Overall Survival (OS)

    Up to 24 months after infusion

  • Module 2: Safety of NT-175 in participants with haematological malignancies

    \- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175

    Up to 28 days after infusion

  • Module 2: Safety of NT-175 in participants with haematological malignancies

    * Incidence of Treatment Emergent Adverse Events (TEAE) * Serious Adverse Events (SAE)

    Up to 24 months after infusion

Secondary Outcomes (2)

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

    Up to 24 months after infusion

  • Module 2: Evaluate preliminary anti-tumour activity in participants with AML or MDS

    Up to 24 months after infusion

Study Arms (1)

NT-175 for advanced malignancies

EXPERIMENTAL

TCR T cell therapy product

Biological: NT-175

Interventions

NT-175BIOLOGICAL

* 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)

NT-175 for advanced malignancies

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • 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
  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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 LungSquamous Cell Carcinoma of Head and NeckColorectal NeoplasmsBreast NeoplasmsOvarian Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeHead and Neck NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Study Officials

  • AstraZeneca

    AstraZeneca

    STUDY DIRECTOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Platform Study
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

July 13, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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.
More information

Locations

US(18)