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Phase 1 Study to Investigate TCRTs KRAS Mutation in Unresectable, Advanced, and/or Metastatic Solid Tumors

NCT06218914 · AstraZeneca
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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
About this study
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.
Eligibility criteria
Key Inclusion Criteria: * 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 Key Exclusion Criteria: * 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.
Study design
Enrollment target: 108 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-03-22
Estimated completion: 2043-11-18
Last updated: 2026-03-09
Interventions
Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12DBiological: AZD0240: Autologous, engineered T Cells targeting KRAS G12D
Primary outcomes
  • Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors (Through study completion, an average of 2 years)
  • Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE) (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 (28 days after infusion)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
All locations (18)
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Duarte, California, United States
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Los Angeles, California, United States
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Newport Beach, California, United States
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Jacksonville, Florida, United States
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Chicago, Illinois, United States
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Westwood, Kansas, United States
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Boston, Massachusetts, United States
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St Louis, Missouri, United States
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New York, New York, United States
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New York, New York, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Nashville, Tennessee, United States
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Dallas, Texas, United States
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Galveston, Texas, United States
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Houston, Texas, United States
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Aberdeen, Washington, United States
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Milwaukee, Wisconsin, United States