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

Launched by ASTRAZENECA · May 17, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called NT-175 for adults with advanced solid tumors, which are types of cancer that cannot be removed by surgery. Specifically, this trial focuses on patients whose tumors have a specific genetic change known as the TP53 R175H mutation and who also have a certain protein (HLA-A*02:01) present in their bodies. The goal is to see if this specially designed therapy can help patients with various cancers, including lung, breast, colorectal, pancreatic, and ovarian cancers, particularly when other treatments have not worked.

To participate in this trial, you must be at least 18 years old and have been diagnosed with one of the eligible cancers that meet the study's criteria. You’ll need to have advanced disease that has not responded to standard treatments, and your tumor must have the right genetic markers. If you qualify, you can expect to receive NT-175, which involves using your own immune cells that have been modified to target your cancer. Throughout the trial, you will undergo regular check-ups to monitor your health and the treatment's effects. It’s important to know that this is an early-stage trial, which means researchers are still learning about how well this treatment works and what side effects it might cause.

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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.