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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05877599
• Other study ID #: NT-175-201
• Status: Recruiting
• Phase: Phase 1
• Start date: July 27, 2023
• Est. completion date: August 2039

Study information

• Verified date: April 2024
• Source: Neogene Therapeutics, Inc.
• Contact: Neogene Medical Affairs
• Phone: (310) 742-9929
• Email: MedicalAffairs[@]neogene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: August 2039
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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
• 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).
• 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.

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Non-small Cell Lung Cancer
• Other Solid Tumors
• Pancreatic Adenocarcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

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)

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Baylor Scott & White Medical Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	Rutgers University	New Brunswick	New Jersey
United States	Hoag Medical Group	Newport Beach	California
United States	Providence Cancer Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Neogene Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175	28 days after infusion
Primary	Adverse events and serious adverse events	Incidence of adverse events and serious adverse events by dose level	Up to 24 months post-infusion
Secondary	Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Secondary	Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Secondary	Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Secondary	Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Secondary	Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion
Secondary	Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors	Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.	Up to 24 months after infusion