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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide * Single infusion TCR T cells * Post-infusion recombinant interleukin-2 (rIL-2)
Research Site
Gilbert, Arizona, United States
RECRUITINGResearch Site
Duarte, California, United States
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
RECRUITINGResearch Site
New Brunswick, New Jersey, United States
RECRUITINGResearch Site
New York, New York, United States
RECRUITING...and 8 more locations
Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Time frame: 28 days after infusion
Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Incidence of adverse events and serious adverse events
Time frame: Up to 24 months post-infusion
Part 2: Further Evaluate the safety of NT-175 at the RP2D in subjects with unresectable, advanced, and/or metastatic solid tumors
Treatment-emergent adverse events, and serios adverse events
Time frame: Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
Time frame: Up to 24 months after infusion
AstraZeneca Clinical Study Information Center
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.