A Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of Sotorasib Plus Trastuzumab Deruxtecan in Patients With Advanced Non-Small Cell Lung Cancer With a KRASG12C Mutation
National Cancer Institute (NCI)
Summary
This phase I/II trial tests the safety, side effects and best dose of sotorasib with trastuzumab deruxtecan and how well the combination works in treating patients with KRAS G12C mutated non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sotorasib blocks a protein made by the mutated KRAS gene (KRAS p.G12C), which may help keep tumor cells from growing and may kill them. It is a type of targeted therapy. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving sotorasib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or effective in treating patients with locally advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation.
Description
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of sotorasib (AMG-510) combined with trastuzumab deruxtecan (DS-8201a) in patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRAS\^G12C mutation who progress on a KRAS\^G12C inhibitor and platinum-based chemotherapy with or without programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PD-L1) inhibitors or PD1/L1 inhibitors alone. (Phase I) II. To determine overall response rate (ORR) defined as the proportion of patients with a confirmed response as per investigator assessment according to…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically or cytologically documented locally advanced or metastatic KRAS\^G12C-mutant NSCLC that has previously been treated with a KRAS\^G12C inhibitor AND an immune checkpoint inhibitor (ICI) AND chemotherapy, either given concurrently or sequentially, UNLESS they have any contra-indications to any drug class described above * Patients must have KRAS\^G12C mutation identified by tumor tissue or plasma circulating tumor deoxyribonucleic acid (ctDNA) profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathol…
Interventions
- ProcedureBiopsy Procedure
Undergo tumor biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT
- ProcedureEchocardiography Test
Undergo ECHO
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- DrugSotorasib
Given PO
Locations (9)
- University of California Davis Comprehensive Cancer CenterSacramento, California
- Moffitt Cancer Center-International PlazaTampa, Florida
- Moffitt Cancer Center - McKinley CampusTampa, Florida
- Moffitt Cancer CenterTampa, Florida
- Moffitt Cancer Center at Wesley ChapelWesley Chapel, Florida
- Case Western Reserve UniversityCleveland, Ohio