TrialPath
← Back to searchRecruiting

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

NCT05877599 · AstraZeneca
In plain English

Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.

Official title
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
About this study
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.
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.
Study design
Enrollment target: 45 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-07-12
Estimated completion: 2029-07-31
Last updated: 2026-04-15
Interventions
Biological: Autologous, engineered T Cells targeting TP53 R175H
Primary outcomes
  • Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors (28 days after infusion)
  • Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors (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 (Up to 24 months after infusion)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
InvestigatorAstraZeneca · study_director, AstraZeneca
All locations (18)
Research SiteRecruiting
Gilbert, Arizona, United States
Research SiteRecruiting
Duarte, California, United States
Research SiteRecruiting
Newport Beach, California, United States
Research SiteRecruiting
Santa Monica, California, United States
Research SiteRecruiting
Jacksonville, Florida, United States
Research SiteWithdrawn
Miami, Florida, United States
Research SiteWithdrawn
Tampa, Florida, United States
Research SiteRecruiting
Boston, Massachusetts, United States
Research SiteRecruiting
New Brunswick, New Jersey, United States
Research SiteRecruiting
New York, New York, United States
Research SiteWithdrawn
Charlotte, North Carolina, United States
Research SiteWithdrawn
Winston-Salem, North Carolina, United States
Research SiteRecruiting
Portland, Oregon, United States
Research SiteRecruiting
Pittsburgh, Pennsylvania, United States
Research SiteRecruiting
Nashville, Tennessee, United States
Research SiteRecruiting
Houston, Texas, United States
Research SiteRecruiting
Round Rock, Texas, United States
Research SiteRecruiting
Milwaukee, Wisconsin, United States
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 · TrialPath