RecruitingPhase 1NCT06218914

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

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


Sponsor

AstraZeneca

Enrollment

108 participants

Start Date

Mar 22, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria6

  • 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

Exclusion Criteria10

  • 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.

Interventions

BIOLOGICALNT-112: Autologous, engineered T Cells targeting KRAS G12D

NT-112 targets KRAS G12D in the context of HLA-C\*08:02

BIOLOGICALAZD0240: Autologous, engineered T Cells targeting KRAS G12D

AZD0240 targets KRAS G12D in the context of HLA-A\*11:01 or HLA-A\*11:02


Locations(18)

Research Site

Duarte, California, United States

Research Site

Los Angeles, California, United States

Research Site

Newport Beach, California, United States

Research Site

Jacksonville, Florida, United States

Research Site

Chicago, Illinois, United States

Research Site

Westwood, Kansas, United States

Research Site

Boston, Massachusetts, United States

Research Site

St Louis, Missouri, United States

Research Site

New York, New York, United States

Research Site

New York, New York, United States

Research Site

Philadelphia, Pennsylvania, United States

Research Site

Pittsburgh, Pennsylvania, United States

Research Site

Nashville, Tennessee, United States

Research Site

Dallas, Texas, United States

Research Site

Galveston, Texas, United States

Research Site

Houston, Texas, United States

Research Site

Aberdeen, Washington, United States

Research Site

Milwaukee, Wisconsin, United States

View Full Details on ClinicalTrials.gov

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NCT06218914


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