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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06218914
• Other study ID #: NT-112-301
• Status: Recruiting
• Phase: Phase 1
• Start date: February 5, 2024
• Est. completion date: January 2, 2040

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-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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: January 2, 2040
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Endometrial Cancer
• Endometrial Neoplasms
• KRAS G12D
• Non-small Cell Lung Cancer
• Pancreatic Ductal Adenocarcinoma
• Solid Tumor, Adult

Intervention

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)

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	NYU Langone Health	New York	New York

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	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))	Incidence of dose-limiting toxicities	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-112 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 post-infusion
Secondary	Preliminary anti-tumor activity of NT-112 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 post-infusion
Secondary	Preliminary anti-tumor activity of NT-112 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 post-infusion
Secondary	Preliminary anti-tumor activity of NT-112 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 post-infusion
Secondary	Preliminary anti-tumor activity of NT-112 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 post-infusion
Secondary	Preliminary anti-tumor activity of NT-112 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 post-infusion
Secondary	Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors	Overall survival (OS)	Up to 24 months post-infusion