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.
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.
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.
Sequential
NT-112: Autologous, engineered T Cells targeting KRAS G12D
Biological/VaccineNT-112 targets KRAS G12D in the context of HLA-C\*08:02
AZD0240: Autologous, engineered T Cells targeting KRAS G12D
Biological/VaccineAZD0240 targets KRAS G12D in the context of HLA-A\*11:01 or HLA-A\*11:02
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)
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)
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)
Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, determined by Investigator assessment * Best objective response (BOR) * Duration of response (DOR) * Clinical benefit rate (CBR) (complete response \[CR\], partial response \[PR\], stable disease \[SD\]) * Time to response (TTR) * Progression-free survival (PFS) * Overall survival (OS)
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
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, determined by Investigator assessment * Best objective response (BOR) * Duration of response (DOR) * Clinical benefit rate (CBR) (complete response \[CR\], partial response \[PR\], stable disease \[SD\]) * Time to response (TTR) * Progression-free survival (PFS) * Overall survival (OS)
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