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
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Eligibility Criteria
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 …
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.
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