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

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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 Design

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

Arm Groups

ArmDescriptionAssigned Intervention
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)

Recruiting Locations

University of Kansas Cancer Center - Westwood Campus
Fairway, Kansas 66205
Contact:
Nurse Navigation Line
913-945-7552
CTNurseNav@kumc.edu

More Details

Status
Recruiting
Sponsor
Neogene Therapeutics, Inc.

Study Contact

Neogene Medical Affairs
(310) 742-9929
NT-112-301-clinical@neogene.com

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.