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

Sponsor
Neogene Therapeutics, Inc. (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05877599
Collaborator
(none)
24
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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
  • Biological: Autologous, engineered T Cells targeting TP53 R175H
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

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Aug 1, 2023
Anticipated Primary Completion Date :
Aug 1, 2026
Anticipated Study Completion Date :
Aug 1, 2039

Arms and Interventions

Arm Intervention/Treatment
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)

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
  • 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 (confirmed by an FDA-approved test), and subject must be HLA-A*02:01 positive (at least 1 allele).

  • 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

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.

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Neogene Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT05877599
Other Study ID Numbers:
  • NT-175-201
First Posted:
May 26, 2023
Last Update Posted:
May 26, 2023
Last Verified:
May 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 26, 2023