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

Purpose

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.

Conditions

  • Non-small Cell Lung Cancer
  • Colorectal Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Endometrial Cancer
  • Solid Tumor, Adult
  • KRAS G12D

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

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

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NT-112 		Part A Dose Escalation and Part B Dose Expansion of NT-112
  • Biological: NT-112: Autologous, engineered T Cells targeting KRAS G12D
    NT-112 targets KRAS G12D in the context of HLA-C*08:02
Experimental
AZD0240 		Part A Dose Escalation and Part B Dose Expansion of AZD0240
  • Biological: AZD0240: Autologous, engineered T Cells targeting KRAS G12D
    AZD0240 targets KRAS G12D in the context of HLA-A*11:01 or HLA-A*11:02

Recruiting Locations

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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.