Trial Title:
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
NCT ID:
NCT05877599
Condition:
Non-small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Colorectal Carcinoma
Pancreatic Adenocarcinoma
Breast Cancer
Other Solid Tumors
Ovarian Cancer
Conditions: Official terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Adenocarcinoma
Ovarian Neoplasms
Squamous Cell Carcinoma of Head and Neck
Colorectal Neoplasms
Conditions: Keywords:
Cell therapy
TP53
Solid tumors
Non-small cell lung cancer
Head and neck squamous cell carcinoma
Colorectal carcinoma
Pancreatic adenocarcinoma
Breast Cancer
Ovarian Cancer
TCR
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Autologous, engineered T Cells targeting TP53 R175H
Description:
- Pre-conditioning by non-myeloablative chemotherapy with fludarabine and
cyclophosphamide
- Single infusion TCR T cells
- Post-infusion recombinant interleukin-2 (rIL-2)
Arm group label:
Dose Escalation and Expansion
Arm group label:
Part 1: Disease Histology Evaluation
Arm group label:
Part 2: Disease Cohort Expansion
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.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria
- Subjects must be at least 18 years of age, at the time of signing the informed
consent.
- Subjects must be capable of giving signed informed consent.
- 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) as confirmed by an CLIA-accredited laboratory-based
test.
- 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 per computed tomography (CT) scan or
magnetic resonance imaging (MRI) per RECIST version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time
of enrollment
- Adequate hematological, renal, hepatic, pulmonary, and cardiac function
- Per Investigator judgement, subject is likely to complete study visits and/or
procedures per the protocol and comply with study requirements for study
participation
Key Exclusion Criteria
- Any another primary malignancy within the 3 years prior to enrollment (except for
non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or
low-grade prostate cancer
- 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 stroke or transient ischemic attack within the 12 months prior to
enrollment.
- 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.
- History of severe immediate hypersensitivity reaction to cyclophosphamide,
fludarabine, or rIL-2; or known sensitivity or allergy to methotrexate, gentamicin,
or other aminoglycosides.
- Any form of primary immunodeficiency.
- Live vaccine ≤ 4 weeks prior to enrollment or plans to have a live vaccine prior to
planned lymphodepleting chemotherapy and/or NT-175 treatment.
- Active immune-mediated disease requiring systemic steroids or other
immunosuppressive treatment (except if related to prior checkpoint inhibitor
therapy)
- Female of childbearing potential who is lactating or breast feeding at the time of
enrollment.
- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed
with Li-Fraumeni syndrome.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marwan Fakih, Dr.
Phone:
(626) 256-4673
Email:
mfakih@coh.org
Facility:
Name:
University of California, Los Angeles (UCLA)
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Chris Hannigan
Phone:
(310) 825-4493
Email:
CHannigan@mednet.ucla.edu
Facility:
Name:
Hoag Medical Group
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Status:
Recruiting
Contact:
Last name:
Chi Nguyen
Phone:
(949) 764-5543
Email:
Chi.Nguyen@hoag.org
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rishi Surana, MD
Email:
rishi_surana@dfci.harvard.edu
Contact backup:
Last name:
Quentin Berry
Email:
quentin_berry@dfci.harvard.edu
Facility:
Name:
Rutgers University
Address:
City:
New Brunswick
Zip:
09803
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kassie Diorio
Email:
kassie.diorio@rutgers.edu
Facility:
Name:
Providence Cancer Institute
Address:
City:
Portland
Zip:
97225
Country:
United States
Status:
Recruiting
Contact:
Last name:
Providence Cancer Institute
Email:
CanRsrchStudies@providence.org
Facility:
Name:
Sarah Cannon Research Institute (SCRI) Oncology Partners
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Director
Email:
scri.ddureferrals@scri.com
Facility:
Name:
Baylor Scott & White Medical Center
Address:
City:
Dallas
Zip:
75246
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Director
Email:
corcsolidtumor@BSWHealth.org
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ecaterina Dumbrava
Email:
EEIleana@mdanderson.org
Contact backup:
Last name:
Miriam Gavriliuc
Email:
mailto:MNGavriliuc@mdanderson.org
Start date:
July 27, 2023
Completion date:
August 2039
Lead sponsor:
Agency:
Neogene Therapeutics, Inc.
Agency class:
Industry
Source:
Neogene Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05877599
