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

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 solid tumors.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

Key Inclusion Criteria

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

Key Exclusion Criteria

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.