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

Phase 1

Recruiting

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

• Registration Number: NCT06218914
• Lead Sponsor: AstraZeneca

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.

Study Timeline

• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-18
• Study First Posted: 2024-01-23
• Study Start: 2024-03-22
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-29
• Last Update Posted: 2025-09-30
• Primary Completion: 2027-08-30
• Study Completion: 2044-04-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Research Site; 🇺🇸 Milwaukee, Wisconsin, United States