A Study of NT-112 in HLA-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/ or Metastatic Solid Tumors Positive for the KRAS G12D Mutation

April 1, 2024 updated by: Neogene Therapeutics, Inc.

An Open-label, Phase 1, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor Activity of NT-112 in Human Leukocyte Antigen-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for the KRAS G12D Mutation

Phase I Study of NT-112, an autologous T-cell therapy product genetically engineered to express an HLA-C*08:02-restricted T cell receptor (TCR), targeting KRAS G12D mutant solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1, open-label, multicenter study to evaluate the safety and preliminary antitumor activity of NT-112 in HLA-C*08:02 subjects with unresectable, advanced, and/or metastatic NSCLC, colorectal adenocarcinoma, pancreatic adenocarcinoma, endometrial cancer, or any other solid tumor histology that is positive for the KRAS G21D mutation.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Marwan Fakih, MD
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health
        • Principal Investigator:
          • Salman Punekar, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Age ≥18 years
  • Diagnosed with NSCLC, Colorectal adenocarcinoma, Pancreatic adenocarcinoma, Endometrial Cancer or any other solid tumor
  • Tumors must harbor a KRAS G12D variant mutation and subject must be HLA-C*08:02 positive
  • 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.
  • Presence of at least 1 measurable lesion per RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment

Key Exclusion Criteria:

  • Any other 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.
  • Any form of primary immunodeficiency.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NT-112
Dose Escalation of NT-112.
Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12D
  • Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
  • Single infusion of T cell receptor (TCR) T cells
  • Post-infusion recombinant interleukin-2 (rIL-2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the safety of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors; evaluation of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D(s))
Time Frame: 28 days after infusion
Incidence of dose-limiting toxicities
28 days after infusion
Adverse events and Serious adverse events
Time Frame: Up to 24 months post-infusion
Incidence of adverse events and serious adverse events by dose level
Up to 24 months post-infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
Up to 24 months post-infusion
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Best Overall Response (BOR) per RECIST V1.1 determined by Investigator assessment.
Up to 24 months post-infusion
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Duration of Response (DOR) per RECIST V1.1 determined by Investigator assessment.
Up to 24 months post-infusion
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Clinical Benefit Rate (CBR) per RECIST V1.1 determined by Investigator assessment.
Up to 24 months post-infusion
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Time to Response (TTR) per RECIST V1.1 determined by Investigator assessment.
Up to 24 months post-infusion
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Progression-free survival (PFS) per RECIST V1.1 determined by Investigator assessment.
Up to 24 months post-infusion
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
Time Frame: Up to 24 months post-infusion
Overall survival (OS)
Up to 24 months post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neogene Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2024

Primary Completion (Estimated)

August 30, 2025

Study Completion (Estimated)

January 2, 2040

Study Registration Dates

First Submitted

January 9, 2024

First Submitted That Met QC Criteria

January 18, 2024

First Posted (Actual)

January 23, 2024

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

April 1, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NT-112-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Endometrial Cancer

Clinical Trials on NT-112: Autologous, engineered T Cells targeting KRAS G12D

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kosovo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe