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Recruiting Phase 1

A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

NCT05877599 · tracked via the Priya Life Science USA tracker
Phase
Phase 1
Started
2023-07-12
Last updated
2026-09-29

Condition(s) studied

Non-small Cell Lung CancerHead and Neck Squamous Cell CarcinomaColorectal CarcinomaPancreatic AdenocarcinomaBreast CancerOther Solid TumorsOvarian CancerMyeloid Neoplasms (AML/MDS)

Investigational drug(s) / intervention(s)

NT-175

NT-175: * 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)

Study 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

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria (Module 1) * 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 Key Exclusion Criteria (Module 1) * 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. Key Inclusion Criteria (Module 2 - hematological malignancies) * 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 Key Exclusion Criteria (Module 2 - hematological malignancy) * 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 * History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells * Prior stroke, ischemic attack, significant cardiac disease, heart failure * Prior adoptive modified cell therapy * Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Primary outcome measure(s)

  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours — 28 days after infusion
    Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours — Up to 24 months post-infusion
    Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)
  • Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours — Up to 24 months after infusion
    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)
  • Module 2: Safety of NT-175 in participants with haematological malignancies — Up to 28 days after infusion
    \- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
  • Module 2: Safety of NT-175 in participants with haematological malignancies — Up to 24 months after infusion
    * Incidence of Treatment Emergent Adverse Events (TEAE) * Serious Adverse Events (SAE)

Trial sites (20)

FacilityCityRegionStatus
Research Site Gilbert Arizona Recruiting
Research Site Duarte California Recruiting
Research Site Los Angeles California Recruiting
Research Site Newport Beach California Recruiting
Research Site Santa Monica California Recruiting
Research Site Jacksonville Florida Recruiting
Research Site Miami Florida Withdrawn
Research Site Tampa Florida Withdrawn
Research Site Boston Massachusetts Recruiting
Research Site Boston Massachusetts Recruiting
Research Site New Brunswick New Jersey Recruiting
Research Site New York New York Recruiting
Research Site Charlotte North Carolina Withdrawn
Research Site Winston-Salem North Carolina Withdrawn
Research Site Portland Oregon Recruiting
Research Site Pittsburgh Pennsylvania Recruiting
Research Site Nashville Tennessee Recruiting
Research Site Houston Texas Recruiting
Research Site Round Rock Texas Recruiting
Research Site Milwaukee Wisconsin Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05877599 on ClinicalTrials.gov ↗ ← All trials in the USA