Colorectal Carcinoma, Endometrial Cancer, KRAS G12D, Non-small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Solid Tumor, Adult
Conditions
Keywords
TCR-T cell therapy, KRAS, KRAS G12D, Autologous, PDAC, NSCLC, Colorectal Cancer, Solid tumors, Pancreatic Ductal Adenocarcinoma, HLA-C*08:02, HLA-A*11:01, HLA-A*11:02
Brief 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.
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
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) | 28 days after infusion | 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 | 28 days after infusion | Incidence of DLTs, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors | Up to 24 months post-infusion | 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 | Up to 24 months post infusion | 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) |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed