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RecruitingInterventionalPhase 1

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

NCT ID: NCT06218914Sponsor: AstraZenecaLast updated: 2026-05-28

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.

Detailed description

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.

Arms & 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

Outcome measures

Primary

  • Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors

    Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Time frame: Through study completion, an average of 2 years

  • Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE)

    Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Time frame: 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

    Incidence of DLTs, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)

    Time frame: 28 days after infusion

Secondary

  • Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors

    Time frame: Up to 24 months post-infusion

  • Part B (Dose Expansion): Evaluate the preliminary anti-tumor activity of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors

    Time frame: Up to 24 months post infusion

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (18)

Research Site

Duarte, California, 91010

Recruiting

Research Site

Los Angeles, California, 90095

Recruiting

Research Site

Newport Beach, California, 92663

Recruiting

Research Site

Jacksonville, Florida, 32224

Recruiting

Research Site

Chicago, Illinois, 60637

Recruiting

Research Site

Westwood, Kansas, 66205

Recruiting

Research Site

Boston, Massachusetts, 02115

Recruiting

Research Site

St Louis, Missouri, 63110

Recruiting

Research Site

New York, New York, 10016

Recruiting

Research Site

New York, New York, 10065

Not Yet Recruiting

Research Site

Portland, Oregon, 97213

Recruiting

Research Site

Philadelphia, Pennsylvania, 19107

Recruiting

Research Site

Pittsburgh, Pennsylvania, 15237

Recruiting

Research Site

Nashville, Tennessee, 37203

Recruiting

Research Site

Dallas, Texas, 75246

Recruiting

Research Site

Galveston, Texas, 77555

Recruiting

Research Site

Houston, Texas, 77030

Recruiting

Research Site

Milwaukee, Wisconsin, 53226

Recruiting