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 identifier:NT-175-201

ClinicalTrials.gov identifier:NCT05877599

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

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

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 1

Healthy volunteers

Study drug

Sex

All

Estimated Enrollment

162

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 27 Jul 2023

Estimated Primary Completion Date: 01 Sept 2028

Estimated Study Completion Date: 01 Aug 2039

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2024 by AstraZeneca

Collaborators

AstraZeneca

Inclusion and exclusion criteria

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:
o NSCLC
o Colorectal adenocarcinoma
o HNSCC
o Pancreatic adenocarcinoma
o Breast cancer
o Ovarian cancer
o 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.

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No locations available

Arms	Assigned Interventions
Experimental: Dose Escalation and Expansion Dose Escalation of TCR T cell product	Biological/Vaccine: 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)
Experimental: Part 1: Disease Histology Evaluation TCR T Cell Product at the MTD	Biological/Vaccine: 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)
Experimental: Part 2: Disease Cohort Expansion TCR T Cell Product at the RP2D	Biological/Vaccine: 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)

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator