Non-small Cell Lung CancerPhase 1NCT05877599
A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation
A Phase 1 study testing NT-175 in people with Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma, run by AstraZeneca at 20 sites in United States.
Trial summary
Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Carcinoma
- What is being tested?
- NT-175
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 20 sitesUnited States
- Study dates
- 12 Jul 2023to 31 Jul 2029
- 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
- Subjects must be at least 18 years of age
- Subject must be diagnosed with one of the histologies below:
- NSCLC
- Colorectal adenocarcinoma
- HNSCC
- Pancreatic adenocarcinoma
Show all 14Show fewer
- Breast cancer
- Ovarian cancer
- Any other solid tumor
- Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A*02:01 positive (at least 1 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.
- Subject has at least 1 measurable lesion
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Adequate hematological, renal, hepatic, pulmonary, and cardiac function
Who cannot join
- Any another primary malignancy within the 3 years prior to enrollment
- 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 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.
Show all 21Show fewer
- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
- Key Inclusion Criteria (Module 2 - hematological malignancies)
- At least 18 years of age
- Diagnosis of AML or MDS that allows for efficacy assessments
- Confirmation of TP53 R175H variant mutation in cancer cells
- Subject must be HLA-A*02:01 positive (at least 1 allele)
- ECOG performance status of 0 to 1
- Key Exclusion Criteria (Module 2 - hematological malignancy)
- Acute promyelocytic leukaemia or isolated extramedullary disease
- Another primary malignancy within 2 years (with exceptions)
- HSCT within 100 days or immunosuppression for GvHD within 4 weeks
- History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells
- Prior stroke, ischemic attack, significant cardiac disease, heart failure
- Prior adoptive modified cell therapy
- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
20 sites in 1 country
United States20 sites, 16 recruiting
- Recruiting
Research Site
Boston, Massachusetts, 02115
- Recruiting
Research Site
Boston, Massachusetts, 02215
- Withdrawn
Research Site
Charlotte, North Carolina, 28204
- Recruiting
Research Site
Duarte, California, 91010
- Recruiting
Research Site
Gilbert, Arizona, 85234
- Recruiting
Research Site
Houston, Texas, 77030
- Recruiting
Research Site
Jacksonville, Florida, 32224
- Recruiting
Research Site
Los Angeles, California, 90095
- Withdrawn
Research Site
Miami, Florida, 33136
- Recruiting
Research Site
Milwaukee, Wisconsin, 53226
- Recruiting
Research Site
Nashville, Tennessee, 37203
- Recruiting
Research Site
New Brunswick, New Jersey, 08901
- Recruiting
Research Site
New York, New York, 10065
- Recruiting
Research Site
Newport Beach, California, 92663
- Recruiting
Research Site
Pittsburgh, Pennsylvania, 15232
- Recruiting
Research Site
Portland, Oregon, 97213
- Recruiting
Research Site
Round Rock, Texas, 78665
- Recruiting
Research Site
Santa Monica, California, 90404
- Withdrawn
Research Site
Tampa, Florida, 33612
- Withdrawn
Research Site
Winston-Salem, North Carolina, 27103
About this study
Official title: An Open-label, Phase 1, Multicentre Platform Study to Evaluate the Safety and Preliminary Anti-tumour Activity of NT-175 in Human Leukocyte Antigen-A*02:01-Positive Adult Participants With Advanced Malignancies That Are Positive for the TP53 R175H Mutation
Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies
Read the detailed description
This is a Phase 1, open-label, multicentre platform study to evaluate the safety and preliminary antitumour activity of NT-175 in HLA-A*02:01 participants with advanced malignancies that are positive for the TP53 R175H mutation.
Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D.
Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at or below the MTD in disease specific histologies and determine the RP2D.
Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of NT-175 at the RP2D in disease specific settings.
- Conditions
- Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Carcinoma, Pancreatic Adenocarcinoma, Breast Cancer, Other Solid Tumors
- Being tested
- NT-175
- Keywords
- Cell therapy, TP53, Solid tumors, Non-small cell lung cancer, Head and neck squamous cell carcinoma, Colorectal carcinoma, Pancreatic adenocarcinoma, Breast Cancer, Ovarian Cancer, AML, MDS, TCR
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Colorectal Neoplasms, Breast Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NT-175Biological
- Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
- Single infusion Autologous, engineered T Cells targeting TP53 R175H
- Post-infusion recombinant interleukin-2 (rIL-2)
| Study group | Role | What they receive |
|---|---|---|
| NT-175 for advanced malignancies | Experimental | TCR T cell therapy product Receives: Biological: NT-175 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Measured: 28 days after infusion
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)
Measured: Up to 24 months post-infusion
Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Per RECIST v1.1 determined by Investigator assessment:
- Objective Response Rate (ORR)
- Best Overall Response (BOR)
- Duration of Response (DOR)
- Clinical Benefit Rate (CBR)
- Time to Response (TTR)
- Progression-free survival (PFS)
- Overall Survival (OS)
Measured: Up to 24 months after infusion
Module 2: Safety of NT-175 in participants with haematological malignancies
- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Measured: Up to 28 days after infusion
Module 2: Safety of NT-175 in participants with haematological malignancies
- Incidence of Treatment Emergent Adverse Events (TEAE)
- Serious Adverse Events (SAE)
Measured: Up to 24 months after infusion
Secondary outcomes (2)
Module 1, Part 1: Preliminary anti-tumor activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Per RECIST v1.1 determined by Investigator assessment:
- Objective Response Rate (ORR)
- Best Overall Response (BOR)
- Duration of Response (DOR)
- Clinical Benefit Rate (CBR)
- Time to Response (TTR)
- Progression-free survival (PFS)
- Overall Survival (OS)
Measured: Up to 24 months after infusion
Module 2: Evaluate preliminary anti-tumour activity in participants with AML or MDS
Per ELN 2022 criteria for AML and per IWG 2023 criteria for MDS by Investigator assessment:
- Objective Response Rate (ORR)
- Time to Response (TTR)
- Duration of Response (DOR)
- Event-free survival (EFS)
By Investigator assessment:
- Transfusion Independence (TI)
- Overall Survival (OS)
- Complete Response (CR) + Complete response with partial haematological recover (CRh)
- Complete Response with limited count recovery (CRL) (CRuni + CRbi) in MDS
- MDS time to Progression to AML
- Proportion of participants with subsequent Haematopoietic Stem Cell Transplantation (HSCT)
Measured: Up to 24 months after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2023
- Study start12 Jul 2023
- Primary completion31 Jul 2029 (estimated)
- Study completion31 Jul 2029 (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
- Single group
- Model description
- Platform Study
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AstraZeneca, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05877599
- Sponsor's protocol ID
- NT-175-201
- Other IDs
- D8690C00001
- Status last verified
- Sep 2026
- First submitted
- 17 May 2023
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 1, Multicentre Platform Study to Evaluate the Safety and Preliminary Anti-tumour Activity of NT-175 in Human Leukocyte Antigen-A*02:01-Positive Adult Participants With Advanced Malignancies That Are Positive for the TP53 R175H Mutation
- ClinicalTrials.gov ID
- NCT05877599
- Acronym / sponsor ID
- NT-175-201
- Conditions
- Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Colorectal Carcinoma, Pancreatic Adenocarcinoma, Breast Cancer, Other Solid Tumors
- Keywords
- Cell therapy, TP53, Solid tumors, Non-small cell lung cancer, Head and neck squamous cell carcinoma, Colorectal carcinoma, Pancreatic adenocarcinoma, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2023 (actual)
- Primary completion
- 31 Jul 2029 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 26 May 2023 (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 of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies
Detailed description
This is a Phase 1, open-label, multicentre platform study to evaluate the safety and preliminary antitumour activity of NT-175 in HLA-A*02:01 participants with advanced malignancies that are positive for the TP53 R175H mutation.
Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D.
Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at or below the MTD in disease specific histologies and determine the RP2D.
Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of NT-175 at the RP2D in disease specific settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Platform Study
| Arm | Type | Receives |
|---|---|---|
| NT-175 for advanced malignancies | Experimental | Biological: NT-175TCR T cell therapy product |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subjects must be at least 18 years of age
- Subject must be diagnosed with one of the histologies below:
- Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A*02:01 positive (at least 1 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.
- Subject has at least 1 measurable lesion
Key exclusion criteria (21 listed)
- Any another primary malignancy within the 3 years prior to enrollment
- 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 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.
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-175* Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide * Single infusion Autologous, engineered T Cells targeting TP53 R175H * Post-infusion recombinant interleukin-2 (rIL-2) | Biological | NT-175 for advanced malignancies |
Primary outcome
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Time frame: 28 days after infusion
Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Time frame: Up to 24 months post-infusion
Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)
Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Time frame: Up to 24 months after infusion
Per RECIST v1.1 determined by Investigator assessment: * Objective Response Rate (ORR) * Best Overall Response (BOR) * Duration of Response (DOR) * Clinical Benefit Rate (CBR) * Time to Response (TTR) * Progression-free survival (PFS) * Overall Survival (OS)
Module 2: Safety of NT-175 in participants with haematological malignancies
Time frame: Up to 28 days after infusion
- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Module 2: Safety of NT-175 in participants with haematological malignancies
Time frame: Up to 24 months after infusion
* Incidence of Treatment Emergent Adverse Events (TEAE) * Serious Adverse Events (SAE)
2 secondary outcomes
Module 1, Part 1: Preliminary anti-tumor activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
Time frame: Up to 24 months after infusion
Module 2: Evaluate preliminary anti-tumour activity in participants with AML or MDS
Time frame: Up to 24 months after 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 29 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
AstraZeneca study director
AstraZeneca
20 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-175 in people with Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma, run by AstraZeneca at 20 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 14 inclusion and 21 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 29 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 20 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?
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours (time frame: 28 days after infusion). The study lists 5 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 29 Sep 2026.