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)
Study 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 malignancies
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria (Module 1)
* Subjects must be at least 18 years of age
* Subject must be diagnosed with one of the histologies below:
* NSCLC
* Colorectal adenocarcinoma
* HNSCC
* Pancreatic adenocarcinoma
* Breast cancer
* Ovarian cancer
* Any other solid tumor
* Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A\*02:01 positive (at least 1 allele)
* Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
* Subject has at least 1 measurable lesion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Adequate hematological, renal, hepatic, pulmonary, and cardiac function
Key Exclusion Criteria (Module 1)
* Any another primary malignancy within the 3 years prior to enrollment
* Known, active primary central nervous system (CNS) malignancy
* History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
* History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
* Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
* Any form of primary immunodeficiency.
* Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
Key Inclusion Criteria (Module 2 - hematological malignancies)
* At least 18 years of age
* Diagnosis of AML or MDS that allows for efficacy assessments
* Confirmation of TP53 R175H variant mutation in cancer cells
* Subject must be HLA-A\*02:01 positive (at least 1 allele)
* ECOG performance status of 0 to 1
Key Exclusion Criteria (Module 2 - hematological malignancy)
* Acute promyelocytic leukaemia or isolated extramedullary disease
* Another primary malignancy within 2 years (with exceptions)
* HSCT within 100 days or immunosuppression for GvHD within 4 weeks
* History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells
* Prior stroke, ischemic attack, significant cardiac disease, heart failure
* Prior adoptive modified cell therapy
* Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
Primary outcome measure(s)
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours — 28 days after infusion Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours — Up to 24 months post-infusion Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)
Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours — Up to 24 months after infusion 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)
Module 2: Safety of NT-175 in participants with haematological malignancies — Up to 28 days after infusion \- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Module 2: Safety of NT-175 in participants with haematological malignancies — Up to 24 months after infusion * Incidence of Treatment Emergent Adverse Events (TEAE)
* Serious Adverse Events (SAE)
Trial sites (23)
Facility
City
Region
Status
Research Site
Gilbert
Arizona
Recruiting
Research Site
Duarte
California
Recruiting
Research Site
Duarte
California
Not Yet Recruiting
Research Site
Los Angeles
California
Not Yet Recruiting
Research Site
Newport Beach
California
Recruiting
Research Site
Santa Monica
California
Recruiting
Research Site
Jacksonville
Florida
Recruiting
Research Site
Miami
Florida
Withdrawn
Research Site
Tampa
Florida
Withdrawn
Research Site
Boston
Massachusetts
Recruiting
Research Site
Boston
Massachusetts
Not Yet Recruiting
Research Site
New Brunswick
New Jersey
Recruiting
Research Site
New York
New York
Recruiting
Research Site
New York
New York
Not Yet Recruiting
Research Site
Charlotte
North Carolina
Withdrawn
Research Site
Winston-Salem
North Carolina
Withdrawn
Research Site
Portland
Oregon
Recruiting
Research Site
Pittsburgh
Pennsylvania
Recruiting
Research Site
Nashville
Tennessee
Recruiting
Research Site
Houston
Texas
Recruiting
Research Site
Houston
Texas
Not Yet Recruiting
Research Site
Round Rock
Texas
Recruiting
Research Site
Milwaukee
Wisconsin
Recruiting
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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