A Phase 1 interventional study of NT-175 in Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma and Colorectal Carcinoma, sponsored by AstraZeneca. Recruiting at 20 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment
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.
Key Inclusion Criteria (Module 1)
Subject must be diagnosed with one of the histologies below:
Key Exclusion Criteria (Module 1)
Key Inclusion Criteria (Module 2 - hematological malignancies)
Key Exclusion Criteria (Module 2 - hematological malignancy)
TCR T cell therapy product
Biological: NT-175
* 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
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
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Carcinoma, Non-Small-Cell Lung→
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