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
Subjects must be at least 18 years of age
NSCLC
Colorectal adenocarcinoma
HNSCC
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.
Single group
NT-175
Biological/Vaccine* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide * Single infusion Autologous, engineered T Cells targeting TP53 R175H * Post-infusion recombinant interleukin-2 (rIL-2)
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)
Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Per RECIST v1.1 determined by Investigator assessment: * Objective Response Rate (ORR) * Best Overall Response (BOR) * Duration of Response (DOR) * Clinical Benefit Rate (CBR) * Time to Response (TTR) * Progression-free survival (PFS) * Overall Survival (OS)
Module 2: Safety of NT-175 in participants with haematological malignancies
\- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Module 1, Part 1: Preliminary anti-tumor activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Per RECIST v1.1 determined by Investigator assessment: * Objective Response Rate (ORR) * Best Overall Response (BOR) * Duration of Response (DOR) * Clinical Benefit Rate (CBR) * Time to Response (TTR) * Progression-free survival (PFS) * Overall Survival (OS)
Module 2: Evaluate preliminary anti-tumour activity in participants with AML or MDS
Per ELN 2022 criteria for AML and per IWG 2023 criteria for MDS by Investigator assessment: * Objective Response Rate (ORR) * Time to Response (TTR) * Duration of Response (DOR) * Event-free survival (EFS) By Investigator assessment: * Transfusion Independence (TI) * Overall Survival (OS) * Complete Response (CR) + Complete response with partial haematological recover (CRh) * Complete Response with limited count recovery (CRL) (CRuni + CRbi) in MDS * MDS time to Progression to AML * Proportion of participants with subsequent Haematopoietic Stem Cell Transplantation (HSCT)
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