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

Research Site
Duarte 5344147, California 5332921 91010

Research Site
Los Angeles 5368361, California 5332921 90095

Research Site
Newport Beach 5376890, California 5332921 92663

Research Site
Chicago 4887398, Illinois 4896861 60637

Research Site
Westwood 4281639, Kansas 4273857 66205

Research Site
St Louis 4407066, Missouri 4398678 63110

Research Site
New York 5128581, New York 5128638 10016

Research Site
Philadelphia 4560349, Pennsylvania 6254927 19107

Research Site
Pittsburgh 5206379, Pennsylvania 6254927 15237

Research Site
Nashville 4644585, Tennessee 4662168 37203

Research Site
Dallas 4684888, Texas 4736286 75246

Research Site
Galveston 4692883, Texas 4736286 77555

Research Site
Houston 4699066, Texas 4736286 77030

Research Site
Aberdeen 5785243, Washington 5815135 98520

Research Site
Milwaukee 5263045, Wisconsin 5279468 53226

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.