Clinical trial NCT06218914: A Study of NT-112 in HLA-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/ or Metastatic Solid Tumors Positive for the KRAS G12D Mutation
Official title: An Open-label, Phase 1, Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor Activity of NT-112 in Human Leukocyte Antigen-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for the KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Colorectal Carcinoma
Pancreatic Ductal Adenocarcinoma
Endometrial Cancer
Solid Tumor, Adult
KRAS G12D
Keywords: TCR-T cell therapy
KRAS
KRAS G12D
Autologous
PDAC
NSCLC
Colorectal Cancer
Solid tumors
Pancreatic Ductal Adenocarcinoma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-01-23
Enrollment: 24
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Phase I Study of NT-112, an autologous T-cell therapy product genetically engineered to express an HLA-C\*08:02-restricted T cell receptor (TCR), targeting KRAS G12D mutant solid tumors.

Detailed description: This is a Phase 1, open-label, multicenter study to evaluate the safety and preliminary antitumor activity of NT-112 in HLA-C\*08:02 subjects with unresectable, advanced, and/or metastatic NSCLC, colorectal adenocarcinoma, pancreatic adenocarcinoma, endometrial cancer, or any other solid tumor histology that is positive for the KRAS G21D mutation.

Eligibility 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
* 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

Primary outcomes:
measure: Evaluate the safety of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors; evaluation of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D(s))
timeFrame: 28 days after infusion
measure: Adverse events and Serious adverse events
timeFrame: Up to 24 months post-infusion
Secondary outcomes:
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
measure: Preliminary anti-tumor activity of NT-112 in subjects with unresectable, advanced, and/or metastatic solid tumors
timeFrame: Up to 24 months post-infusion
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Galveston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Aberdeen
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
Study officials:
References: