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
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
* 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)
Research Site
Gilbert, Arizona, United States
RECRUITINGResearch Site
Duarte, California, United States
RECRUITINGResearch Site
Duarte, California, United States
NOT_YET_RECRUITINGResearch Site
Los Angeles, California, United States
NOT_YET_RECRUITINGResearch Site
Newport Beach, California, United States
RECRUITINGResearch Site
Santa Monica, California, United States
RECRUITINGResearch Site
Jacksonville, Florida, United States
RECRUITINGResearch Site
Miami, Florida, United States
WITHDRAWNResearch Site
Tampa, Florida, United States
WITHDRAWNResearch Site
Boston, Massachusetts, United States
RECRUITING...and 13 more locations
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
Time frame: 28 days after infusion
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)
Time frame: Up to 24 months post-infusion
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)
Time frame: Up to 24 months after infusion
Module 2: Safety of NT-175 in participants with haematological malignancies
\- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Time frame: Up to 28 days after infusion
Module 2: Safety of NT-175 in participants with haematological malignancies
* Incidence of Treatment Emergent Adverse Events (TEAE) * Serious Adverse Events (SAE)
Time frame: Up to 24 months after infusion
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)
Time frame: Up to 24 months after infusion
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)
Time frame: Up to 24 months after infusion
AstraZeneca Clinical Study Information Center
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