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A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

NCT05877599 · AstraZeneca
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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
About this study
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.
Eligibility criteria
Key Inclusion Criteria (Module 1) * 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 * 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 Key Exclusion Criteria (Module 1) * 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. * 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.
Study design
Enrollment target: 45 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-07-12
Estimated completion: 2029-07-31
Last updated: 2026-07-13
Interventions
Biological: NT-175
Primary outcomes
  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours (28 days after infusion)
  • Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours (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 (Up to 24 months after infusion)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
InvestigatorAstraZeneca · study_director, AstraZeneca
All locations (18)
Research SiteRecruiting
Gilbert, Arizona, United States
Research SiteRecruiting
Duarte, California, United States
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Newport Beach, California, United States
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Santa Monica, California, United States
Research SiteRecruiting
Jacksonville, Florida, United States
Research SiteWithdrawn
Miami, Florida, United States
Research SiteWithdrawn
Tampa, Florida, United States
Research SiteRecruiting
Boston, Massachusetts, United States
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New Brunswick, New Jersey, United States
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New York, New York, United States
Research SiteWithdrawn
Charlotte, North Carolina, United States
Research SiteWithdrawn
Winston-Salem, North Carolina, United States
Research SiteRecruiting
Portland, Oregon, United States
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Pittsburgh, Pennsylvania, United States
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Nashville, Tennessee, United States
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Houston, Texas, United States
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Round Rock, Texas, United States
Research SiteRecruiting
Milwaukee, Wisconsin, United States
A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation · TrialPath