Phase 1 Study to Investigate TCRTs KRAS Mutation in Unresectable, Advanced, and/or Metastatic Solid Tumors
Open-label, Phase 1, Multi-Center Master Protocol to Evaluate the Safety and Preliminary Anti-Tumor Activity of TCR-engineered T Cells Recognizing KRAS Mutations in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors
1 other identifier
interventional
108
1 country
18
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 nonsmall-cell-lung-cancer
Started Mar 2024
Longer than P75 for phase_1 nonsmall-cell-lung-cancer
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 9, 2024
CompletedFirst Posted
Study publicly available on registry
January 23, 2024
CompletedStudy Start
First participant enrolled
March 22, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 18, 2043
May 1, 2026
April 1, 2026
3.4 years
January 9, 2024
April 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (2)
Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
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
Up to 24 months post infusion
Study Arms (2)
NT-112
EXPERIMENTALPart A Dose Escalation and Part B Dose Expansion of NT-112
AZD0240
EXPERIMENTALPart A Dose Escalation and Part B Dose Expansion of AZD0240
Interventions
NT-112 targets KRAS G12D in the context of HLA-C\*08:02
AZD0240 targets KRAS G12D in the context of HLA-A\*11:01 or HLA-A\*11:02
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (18)
Research Site
Duarte, California, 91010, United States
Research Site
Los Angeles, California, 90095, United States
Research Site
Newport Beach, California, 92663, United States
Research Site
Jacksonville, Florida, 32224, United States
Research Site
Chicago, Illinois, 60637, United States
Research Site
Westwood, Kansas, 66205, United States
Research Site
Boston, Massachusetts, 02115, United States
Research Site
St Louis, Missouri, 63110, United States
Research Site
New York, New York, 10016, United States
Research Site
New York, New York, 10065, United States
Research Site
Portland, Oregon, 97213, United States
Research Site
Philadelphia, Pennsylvania, 19107, United States
Research Site
Pittsburgh, Pennsylvania, 15237, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Dallas, Texas, 75246, United States
Research Site
Galveston, Texas, 77555, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 9, 2024
First Posted
January 23, 2024
Study Start
March 22, 2024
Primary Completion (Estimated)
August 30, 2027
Study Completion (Estimated)
November 18, 2043
Last Updated
May 1, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.