A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation
Breast Cancer
Cancer-Related Syndrome
Leukemia
Lung Cancer
Myelodysplastic Syndromes (MDS)
Ovarian Cancer
18 Years and older, Male and Female
NT-175-201 (primary)
NCI-2023-04428
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
Objectives
This is a Phase 1, open-label, multicentre platform study to evaluate the safety and
preliminary antitumour activity of NT-175 in HLA-A*02:01 participants with advanced
malignancies that are positive for the TP53 R175H mutation.
Dose Escalation will investigate escalating doses of NT-175 in adult subjects with
eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D.
Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at
or below the MTD in disease specific histologies and determine the RP2D.
Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of
NT-175 at the RP2D in disease specific settings.
Eligibility
- 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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