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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

Primary Purpose

Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous, engineered T Cells targeting TP53 R175H
Sponsored by
Neogene Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • City of HopeRecruiting
  • University of California, Los Angeles (UCLA)Recruiting
  • Hoag Medical GroupRecruiting
  • Dana-Farber Cancer InstituteRecruiting
  • Baylor Scott & White Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation

Arm Description

Dose Escalation of TCR T cell product

Outcomes

Primary Outcome Measures

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
Adverse events and serious adverse events
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
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
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
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
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
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
Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.

Full Information

First Posted
May 17, 2023
Last Updated
October 20, 2023
Sponsor
Neogene Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05877599
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2023 (Actual)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
August 2039 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neogene Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Carcinoma, Pancreatic Adenocarcinoma, Breast Cancer, Other Solid Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Dose Escalation of TCR T cell product
Intervention Type
Biological
Intervention Name(s)
Autologous, engineered T Cells targeting TP53 R175H
Intervention Description
Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide Single infusion TCR T cells Post-infusion recombinant interleukin-2 (rIL-2)
Primary Outcome Measure Information:
Title
Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Time Frame
28 days after infusion
Title
Adverse events and serious adverse events
Description
Incidence of adverse events and serious adverse events by dose level
Time Frame
Up to 24 months post-infusion
Secondary Outcome Measure Information:
Title
Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
Time Frame
Up to 24 months after infusion
Title
Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.
Time Frame
Up to 24 months after infusion
Title
Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.
Time Frame
Up to 24 months after infusion
Title
Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.
Time Frame
Up to 24 months after infusion
Title
Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.
Time Frame
Up to 24 months after infusion
Title
Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors
Description
Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
Time Frame
Up to 24 months after infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 (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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Neogene Medical Affairs
Phone
(310) 742-9929
Email
MedicalAffairs@neogene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Affairs
Organizational Affiliation
Neogene Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marwan Fakih, Dr.
Phone
626-256-4673
Email
mfakih@coh.org
Facility Name
University of California, Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chris Hannigan
Phone
310-825-4493
Email
CHannigan@mednet.ucla.edu
Facility Name
Hoag Medical Group
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chi Nguyen
Phone
949-764-5543
Email
Chi.Nguyen@hoag.org
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Awad, MD
Email
Mark_Awad@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Hope Wei
Email
HopeY_Wei@DFCI.HARVARD.EDU
Facility Name
Baylor Scott & White Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Director
Email
corcsolidtumor@BSWHealth.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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