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
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
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- 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.
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- 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.