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

Inclusion 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:
• o NSCLC
• o Colorectal adenocarcinoma
• o HNSCC
• o Pancreatic adenocarcinoma
• o Breast cancer
• o Ovarian cancer
• o 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.