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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
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.

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
GroupInterventionDescription
Part 1: Disease Histology EvaluationAutologous, engineered T Cells targeting TP53 R175HTCR T Cell Product at the MTD
Dose Escalation and ExpansionAutologous, engineered T Cells targeting TP53 R175HDose Escalation of TCR T cell product
Part 2: Disease Cohort ExpansionAutologous, engineered T Cells targeting TP53 R175HTCR T Cell Product at the RP2D
Primary Outcome Measures
NameTimeMethod
Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumorsUp 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 tumorsUp 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 tumorsUp to 24 months after infusion

Treatment-emergent adverse events, and serios adverse events

Secondary Outcome Measures
NameTimeMethod
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumorsUp to 24 months after infusion

Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.

Trial Locations

Locations (9)

City of Hope

🇺🇸

Duarte, California, United States

University of California, Los Angeles (UCLA)

🇺🇸

Los Angeles, California, United States

Hoag Medical Group

🇺🇸

Newport Beach, California, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Rutgers University

🇺🇸

New Brunswick, New Jersey, United States

Providence Cancer Institute

🇺🇸

Portland, Oregon, United States

Sarah Cannon Research Institute (SCRI) Oncology Partners

🇺🇸

Nashville, Tennessee, United States

Baylor Scott & White Medical Center

🇺🇸

Dallas, Texas, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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