Non-small Cell Lung CancerPhase 1NCT06218914
Phase 1 Study to Investigate TCRTs KRAS Mutation in Unresectable, Advanced, and/or Metastatic Solid Tumors
A Phase 1 study testing NT-112: Autologous, engineered T Cells targeting KRAS G12D and AZD0240: Autologous, engineered T Cells targeting KRAS G12D in people with Non-small Cell Lung Cancer and Colorectal Carcinoma, run by AstraZeneca at 18 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer, Colorectal Carcinoma, Pancreatic Ductal Adenocarcinoma
- What is being tested?
- NT-112: Autologous, engineered T Cells targeting KRAS G12D and AZD0240: Autologous, engineered T Cells targeting KRAS G12D
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 18 sitesUnited States
- Study dates
- 22 Mar 2024to 18 Nov 2043
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
18 sites in 1 country
United States18 sites, 18 recruiting
- Recruiting
Research Site
Boston, Massachusetts, 02115
- Recruiting
Research Site
Chicago, Illinois, 60637
- Recruiting
Research Site
Dallas, Texas, 75246
- Recruiting
Research Site
Duarte, California, 91010
- Recruiting
Research Site
Galveston, Texas, 77555
- Recruiting
Research Site
Houston, Texas, 77030
- Recruiting
Research Site
Jacksonville, Florida, 32224
- Recruiting
Research Site
Los Angeles, California, 90095
- Recruiting
Research Site
Milwaukee, Wisconsin, 53226
- Recruiting
Research Site
Nashville, Tennessee, 37203
- Recruiting
Research Site
New York, New York, 10016
- Recruiting
Research Site
New York, New York, 10065
- Recruiting
Research Site
Newport Beach, California, 92663
- Recruiting
Research Site
Philadelphia, Pennsylvania, 19107
- Recruiting
Research Site
Pittsburgh, Pennsylvania, 15237
- Recruiting
Research Site
Portland, Oregon, 97213
- Recruiting
Research Site
St Louis, Missouri, 63110
- Recruiting
Research Site
Westwood, Kansas, 66205
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Non-small Cell Lung Cancer, Colorectal Carcinoma, Pancreatic Ductal Adenocarcinoma, Endometrial Cancer, Solid Tumor, Adult, KRAS G12D
- Being tested
- NT-112: Autologous, engineered T Cells targeting KRAS G12D, AZD0240: Autologous, engineered T Cells targeting KRAS G12D
- Keywords
- TCR-T cell therapy, KRAS, KRAS G12D, Autologous, PDAC, NSCLC, Colorectal Cancer, Solid tumors, Pancreatic Ductal Adenocarcinoma, HLA-C*08:02, HLA-A*11:01, HLA-A*11:02
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NT-112: Autologous, engineered T Cells targeting KRAS G12DBiological
NT-112 targets KRAS G12D in the context of HLA-C*08:02
AZD0240: Autologous, engineered T Cells targeting KRAS G12DBiological
AZD0240 targets KRAS G12D in the context of HLA-A*11:01 or HLA-A*11:02
| Study group | Role | What they receive |
|---|---|---|
| NT-112 | Experimental | Part A Dose Escalation and Part B Dose Expansion of NT-112 Receives: Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12D |
| AZD0240 | Experimental | Part A Dose Escalation and Part B Dose Expansion of AZD0240 Receives: Biological: AZD0240: Autologous, engineered T Cells targeting KRAS G12D |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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
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)
Measured: 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)
Measured: Up to 24 months post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2024
- Study start22 Mar 2024
- Primary completion30 Aug 2027 (estimated)
- Study completion18 Nov 2043 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06218914
- Sponsor's protocol ID
- NT-112-301
- Status last verified
- Sep 2026
- First submitted
- 9 Jan 2024
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06218914
- Acronym / sponsor ID
- NT-112-301
- Conditions
- Non-small Cell Lung Cancer, Colorectal Carcinoma, Pancreatic Ductal Adenocarcinoma, Endometrial Cancer, Solid Tumor, Adult, KRAS G12D
- Keywords
- TCR-T cell therapy, KRAS, KRAS G12D, Autologous, PDAC, NSCLC, Colorectal Cancer, Solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 22 Mar 2024 (actual)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 18 Nov 2043 (estimated)
- First posted
- 23 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NT-112 | Experimental | Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12DPart A Dose Escalation and Part B Dose Expansion of NT-112 |
| AZD0240 | Experimental | Biological: AZD0240: Autologous, engineered T Cells targeting KRAS G12DPart A Dose Escalation and Part B Dose Expansion of AZD0240 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NT-112: Autologous, engineered T Cells targeting KRAS G12DNT-112 targets KRAS G12D in the context of HLA-C*08:02 | Biological | NT-112 |
| AZD0240: Autologous, engineered T Cells targeting KRAS G12DAZD0240 targets KRAS G12D in the context of HLA-A*11:01 or HLA-A*11:02 | Biological | AZD0240 |
Primary outcome
Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
Time frame: Through study completion, an average of 2 years
Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE)
Time frame: 28 days after infusion
Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Part B (Expansion): Further evaluate the safety of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors
Time frame: 28 days after infusion
Incidence of DLTs, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)
2 secondary outcomes
Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
Time frame: 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
Time frame: Up to 24 months post infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
AstraZeneca Clinical Study Information Center contact
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NT-112: Autologous, engineered T Cells targeting KRAS G12D and AZD0240: Autologous, engineered T Cells targeting KRAS G12D in people with Non-small Cell Lung Cancer and Colorectal Carcinoma, run by AstraZeneca at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors (time frame: Through study completion, an average of 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.