Open Actively Recruiting

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

About

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

Primary Purpose
The main objective of the intervention(s) being evaluated by the clinical trial. Learn more
Treatment
Study Type
The nature of the investigation or investigational use for which clinical study information is being submitted. Learn more
Interventional
Phase
Phase 1

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

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.
Study Stats
Protocol No.
23-000584
Category
Breast Cancer
Colorectal Cancer
Head and Neck Cancer
Lung Cancer
Pancreatic Cancer
Sarcoma
Principal Investigator
J. Randolph Hecht, MD
J. Randolph Hecht, MD
Gastrointestinal Medical Oncology
J. Randolph Hecht, MD
Location
  • UCLA Westwood
For Providers
NCT No.
NCT05877599
For detailed technical eligibility, visit ClinicalTrials.gov.