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
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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, breast cancer, or any other solid tumor histologies that are positive for the TP53 R175H mutation.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Dose Escalation Dose Escalation of TCR T cell product |
Biological: Autologous, 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)
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Outcome Measures
Primary Outcome Measures
- Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [28 days after infusion]
Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
- Adverse events and serious adverse events [Up to 24 months post-infusion]
Incidence of adverse events and serious adverse events by dose level
Secondary Outcome Measures
- Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [Up to 24 months after infusion]
Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
- Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [Up to 24 months after infusion]
Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.
- Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [Up to 24 months after infusion]
Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.
- Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [Up to 24 months after infusion]
Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.
- Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [Up to 24 months after infusion]
Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.
- Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors [Up to 24 months after infusion]
Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
Eligibility Criteria
Criteria
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Subjects must be at least 18 years of age, at the time of signing the informed consent.
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Subjects must be capable of giving signed informed consent
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Subject must be diagnosed with one of the histologies below:
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NSCLC
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Colorectal adenocarcinoma
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HNSCC
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Pancreatic adenocarcinoma
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Breast cancer
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Any other solid tumor
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Tumors must harbor a TP53 R175H variant mutation (confirmed by an FDA-approved test), and subject must be HLA-A*02:01 positive (at least 1 allele).
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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.
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Subject has at least 1 measurable lesion per computed tomography (CT) scan or magnetic resonance imaging (MRI).
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
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Adequate hematological, renal, hepatic, pulmonary, and cardiac function
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Per Investigator judgement, subject is likely to complete study visits and/or procedures per the protocol and comply with study requirements for study participation
Exclusion Criteria:
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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
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Known, active primary central nervous system (CNS) malignancy
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History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
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History of stroke or transient ischemic attack within the 12 months prior to enrollment.
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History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
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Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
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History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or rIL-2; or known sensitivity or allergy to methotrexate, gentamicin, or other aminoglycosides.
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Any form of primary immunodeficiency.
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Live vaccine ≤ 4 weeks prior to enrollment or plans to have a live vaccine prior to planned lymphodepleting chemotherapy and/or NT-175 treatment.
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Active immune-mediated disease requiring systemic steroids or other immunosuppressive treatment (except if related to prior checkpoint inhibitor therapy)
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Female of childbearing potential who is lactating or breast feeding at the time of enrollment.
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Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | City of Hope | Duarte | California | United States | 91010 |
Sponsors and Collaborators
- Neogene Therapeutics, Inc.
Investigators
- Study Director: Ying Yan, MD, Neogene Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NT-175-201