Phase 1 Study To Investigate TCRTs KRAS Mutation In Unresectable, Advanced, And/or Metastatic Solid Tumors

Study Overview

Phase 1 Study to Investigate TCRTs KRAS Mutation in Unresectable, Advanced, and/or Metastatic Solid Tumors

Phase I Study, a master protocol to investigate TCR-Engineered T cells recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.

This is a Phase 1, open-label, Phase 1, Multi-Center Master Protocol to evaluate the safety and preliminary Anti-Tumor activity of TCR-Engineered T cells (KRAS TCRTs) recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.

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

BIOLOGICAL: NT-112: Autologous, engineered T Cells targeting KRAS G12D
BIOLOGICAL: AZD0240: Autologous, engineered T Cells targeting KRAS G12D

NT-112-301

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-01-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-19
First Submitted that Met QC Criteria 2024-01-18	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-08-24
First Posted (ACTUAL) 2024-01-23	Results First Posted N/A	Last Verified 2025-08

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: NT-112 Part A Dose Escalation and Part B Dose Expansion of NT-112	BIOLOGICAL: NT-112: Autologous, engineered T Cells targeting KRAS G12D NT-112 targets KRAS G12D in the context of HLA-C*08:02
EXPERIMENTAL: AZD0240 Part A Dose Escalation and Part B Dose Expansion of AZD0240	BIOLOGICAL: AZD0240: Autologous, engineered T Cells targeting KRAS G12D AZD0240 targets KRAS G12D in the context of HLA-A11:01 or HLA-A11:02

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: NT-112

Part A Dose Escalation and Part B Dose Expansion of NT-112

BIOLOGICAL: NT-112: Autologous, engineered T Cells targeting KRAS G12D

NT-112 targets KRAS G12D in the context of HLA-C*08:02

EXPERIMENTAL: AZD0240

Part A Dose Escalation and Part B Dose Expansion of AZD0240

BIOLOGICAL: AZD0240: Autologous, engineered T Cells targeting KRAS G12D

AZD0240 targets KRAS G12D in the context of HLA-A*11:01 or HLA-A*11:02

Primary Outcome Measures	Measure Description	Time Frame
Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors	Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Through study completion, an average of 2 years
Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE)	Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	28 days after infusion
Part B (Expansion): Further evaluate the safety of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors	Incidence of DLTs, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)	28 days after infusion

Secondary Outcome Measures	Measure Description	Time Frame
Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors	Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, determined by Investigator assessment * Best objective response (BOR) * Duration of response (DOR) * Clinical benefit rate (CBR) (complete response [CR], partial response [PR], stable disease [SD]) * Time to response (TTR) * Progression-free survival (PFS) * Overall survival (OS)	Up to 24 months post-infusion
Part B (Dose Expansion): Evaluate the preliminary anti-tumor activity of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors	Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, determined by Investigator assessment * Best objective response (BOR) * Duration of response (DOR) * Clinical benefit rate (CBR) (complete response [CR], partial response [PR], stable disease [SD]) * Time to response (TTR) * Progression-free survival (PFS) * Overall survival (OS)	Up to 24 months post infusion

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

Name: AstraZeneca Clinical Study Information Center

Phone Number: 1-877-240-9479

Email: information.center@astrazeneca.com

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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, HLA-A*11:01 or HLA-A*11:02 positive in at least one 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.
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

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
Prior treatment with pan-KRAS or KRAS G12D targeting agents unless presence of KRAS G12D mutation is confirmed after the completion of treatment with pan-KRAS or KRAS G12D targeting agents.

Collaborators and Investigators

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

Publications

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