An Open-label, Phase 1, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor Activity of NT-175 in Human Leukocyte Antigen-A*02:01-Positive Adult Subjects With Unresectable, Advanced and/or Metastatic Solid Tumors That Are Positive for the TP53 R175H Mutation
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.
Arms & interventions
- BiologicalAutologous, engineered T Cells targeting TP53 R175H
* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide * Single infusion TCR T cells * Post-infusion recombinant interleukin-2 (rIL-2)
Outcome measures
Primary
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
Secondary
Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
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 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 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 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 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 frame: Up to 24 months after infusion
Eligibility criteria
Study locations (18)
Research Site
Gilbert, Arizona, 85234
Research Site
Duarte, California, 91010
Research Site
Newport Beach, California, 92663
Research Site
Santa Monica, California, 90404
Research Site
Jacksonville, Florida, 32224
Research Site
Miami, Florida, 33136
Research Site
Tampa, Florida, 33612
Research Site
Boston, Massachusetts, 02115
Research Site
New Brunswick, New Jersey, 08901
Research Site
New York, New York, 10065
Research Site
Charlotte, North Carolina, 28204
Research Site
Winston-Salem, North Carolina, 27103
Research Site
Portland, Oregon, 97213
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
Nashville, Tennessee, 37203
Research Site
Houston, Texas, 77030
Research Site
Round Rock, Texas, 78665
Research Site
Milwaukee, Wisconsin, 53226