A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

Phase 1

Recruiting

• Conditions: Head and Neck Squamous Cell Carcinoma; Colorectal Carcinoma; Breast Cancer; Pancreatic Adenocarcinoma; Other Solid Tumors; Non-small Cell Lung Cancer; Ovarian Cancer
• Interventions: Biological: Autologous, engineered T Cells targeting TP53 R175H

• Registration Number: NCT05877599
• Lead Sponsor: AstraZeneca

Brief 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 solid tumors.

Detailed Description

This is a Phase 1, open-label, multicenter study to evaluate the safety and preliminary antitumor activity of NT-175 in HLA-A\*02:01 subjects with unresectable, advanced, and/or metastatic NSCLC, colorectal adenocarcinoma, HNSCC, pancreatic adenocarcinoma, ovarian cancer, breast cancer, or any other solid tumor histologies that are positive for the TP53 R175H mutation.

Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible solid tumor histologies and will evaluate the safety and MTD.

Disease Histology Evaluation will further evaluate the safety and preliminary anti-tumor activity at or below the MTD in disease specific histologies and determine the RP2D. .

Disease Cohort Expansion will further evaluate the preliminary anti-tumor activity and safety of NT-175 at the RP2D in disease specific settings.

Study Timeline

• Study First Submitted: 2023-05-17
• Study First Submitted QC: 2023-05-17
• Study First Posted: 2023-05-26
• Study Start: 2023-07-12
• Status Verified: 2025-08
• Last Update Submitted: 2025-09-22
• Last Update Posted: 2025-09-24
• Primary Completion: 2028-09-01
• Study Completion: 2039-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 1: Disease Histology Evaluation	Autologous, engineered T Cells targeting TP53 R175H	TCR T Cell Product at the MTD
Dose Escalation and Expansion	Autologous, engineered T Cells targeting TP53 R175H	Dose Escalation of TCR T cell product
Part 2: Disease Cohort Expansion	Autologous, engineered T Cells targeting TP53 R175H	TCR T Cell Product at the RP2D

Primary Outcome Measures

Name	Time	Method
Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Up to 24 months post-infusion	Incidence of adverse events and serious adverse events
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Up to 24 months after infusion	Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
Part 2: Further Evaluate the safety of NT-175 at the RP2D in subjects with unresectable, advanced, and/or metastatic solid tumors	Up to 24 months after infusion	Treatment-emergent adverse events, and serios adverse events

Secondary Outcome Measures

Name	Time	Method
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Up to 24 months after infusion	Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.

Trial Locations

Locations (1)

Research Site; 🇺🇸 Milwaukee, Wisconsin, United States