A Phase I Clinical Trial of Carfilzomib in Combination With Sotorasib in Patients With KRASG12C Mutated Advanced Non-Small Cell Lung Cancer
City of Hope Medical Center
Summary
This phase I trial tests the safety, side effects, and best dose of carfilzomib in combination with sotorasib in treating patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Carfilzomib is a drug that binds to and inhibits the activity of the protein complex that is responsible for degrading other damaged or unneeded proteins. The inhibition of this protein by carfilzomib can then cause tumor growth inhibition and cell death. Sotorasib is a drug that binds to and inhibits the activity of the KRAS G12C mutant. This may inhibit growth in KRAS G12C-expressing tumor cells. Combining carfilzomib and sotorasib may be a safe and effective treatment option for patients with KRAS G12C-mutated advanced or metastatic NSCLC.
Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of the combination of carfilzomib and sotorasib in KRAS G12C mutated NSCLC following progression on KRAS inhibitor. II. Describe the safety of the combination of carfilzomib and sotorasib in KRAS G12C mutated NSCLC following progression on KRAS inhibitor. SECONDARY OBJECTIVES: I. Describe clinical responses at all dose levels, including the recommended dose level using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. II. Describe other efficacy endpoints, includi…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Histologically confirmed NSCLC that is metastatic or advanced. The tumor must exhibit evidence of KRASG12C mutation which is determined by either a Clinical Laboratory Improvement Act (CLIA) certified ctDNA assay or by a CLIA certified tumor tissue assay * Measurable disease by RECIST v1.1 * Failed prior KRAS inhibitor * Fully recovered from the acute toxic effects (except alopecia) from prior anti-cancer therapy * Pa…
Interventions
- ProcedureBiopsy
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- DrugCarfilzomib
Given IV
- ProcedureComputed Tomography
Undergo CT
- ProcedureEchocardiography
Undergo ECHO
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugSotorasib
Given PO
Locations (2)
- City of Hope Medical CenterDuarte, California
- City of Hope at Irvine LennarIrvine, California