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

Phase 1

Active, not recruiting

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

• Registration Number: NCT06218914
• Lead Sponsor: AstraZeneca

Brief 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.

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 Timeline

• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-18
• Study First Posted: 2024-01-23
• Study Start: 2024-04-04
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27
• Primary Completion: 2027-08-30
• Study Completion: 2042-08-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Adverse events and Serious adverse events	Up to 24 months post-infusion	Incidence of adverse events and serious adverse events by dose level
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))	28 days after infusion	Incidence of dose-limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors	Up to 24 months post-infusion	Overall survival (OS)

Trial Locations

Locations (1)

Research Site; 🇺🇸 Milwaukee, Wisconsin, United States