Carfilzomib and Sotorasib for KRAS G12C-Mutated Lung Cancer
This study is testing the safety and best dose of two drugs, carfilzomib and sotorasib, when given together to people with advanced or metastatic (spread to other parts of the body) non-small cell lung cancer. Your cancer must have a specific change called a KRAS G12C mutation to be eligible. Carfilzomib works by stopping a protein that helps cancer cells grow, and sotorasib targets the KRAS G12C mutation. Researchers will be looking for how many side effects occur and how severe they are, especially in the first month of treatment. This study aims to find the safest and most effective dose of this drug combination.
- Study design
- This is a dose-escalation study, meaning the dose of carfilzomib will be gradually increased to find the safest and most effective amount. It plans to enroll 15 participants.
- What's involved
- You would receive carfilzomib through an IV (into a vein) on specific days and take sotorasib by mouth daily. You would also undergo biopsies, blood draws, CT scans, and echocardiograms (heart ultrasounds).
- Compensation
- Not stated in the trial record.
- Follow-up
- Researchers will track treatment-related side effects for up to 30 days after you finish the study treatment.
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NCT06249282
Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer
Recruiting
PHASE1Ages 18+InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~15 participants
Updated 2026-04-03 on ClinicalTrials.gov
What's tested:BiopsyBiospecimen CollectionCarfilzomibComputed TomographyEchocardiographyMagnetic Resonance Imaging
At a glance
Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of dose limiting toxicities
Measured over During cycle 1 (each cycle is 28 days)
+1 more outcome measured
Conditions
Where it's being run
2 sites across 1 statesCalifornia2
Study leadership
- Ravi Salgia, MD · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
- Jyoti Malhotra, MD (Co-PI) · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required during the first cycle of therapy
Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (performed within 14 days prior to day 1 of protocol therapy)
NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
Hemoglobin (Hb) ≥ 9 g/dL (performed within 14 days prior to day 1 of protocol therapy)
Platelets ≥ 100,000/mm\^3 (performed within 14 days prior to day 1 of protocol therapy)
NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 14 days prior to day 1 of protocol therapy)
Aspartate aminotransferase (AST) ≤ 3 x ULN (or ≤ 5 x ULN in the setting of liver metastatic disease) (performed within 14 days prior to day 1 of protocol therapy)
Alanine aminotransferase (ALT) ≤ 5 x ULN (or ≤ 5 x ULN in the setting of liver metastatic disease) (performed within 14 days prior to day 1 of protocol therapy)
Creatinine clearance of ≤ 1.5 x ULN or glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 (performed within 14 days prior to day 1 of protocol therapy)
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (performed within 14 days prior to day 1 of protocol therapy)
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 120 days after the last dose of protocol therapy.
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion
Chemotherapy or immunotherapy within 21 days prior to day 1 of protocol therapy
Radiation therapy within 14 days prior to day 1 of protocol therapy
KRAS inhibitor within 14 days prior to day 1 of protocol therapy
Investigational therapy within 28 days prior to day 1 of protocol therapy (or 5 half-lives, use whichever is shorter)
Inability to previously tolerate (240 mg, QD) sotorasib
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Clinically significant uncontrolled illness
Evidence of chronic hepatitis B virus (HBV) infection and HBV viral load detectable
Evidence of untreated chronic hepatitis C virus (HCV) infection. Patients with HCV infection currently on treatment are eligible if they have an undetectable HCV viral load
Active infection requiring antibiotics (not to be completed by day 1 of protocol therapy)
Known history of immunodeficiency virus (HIV) with detectable viral load
Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
New York Heart Association (NYHA) class III or IV heart failure, myocardial infarction in the preceding 6 months, conduction abnormalities uncontrolled by medications
Females only: Pregnant or breastfeeding
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
What this trial measures
- Incidence of dose limiting toxicitiesDuring cycle 1 (each cycle is 28 days)
The incidence of dose-limiting toxicities during cycle 1 will be used to determine the maximum tolerated dose and the recommended phase II dose of the comibination of carfilzomib and sotorasib. Will be described and graded at all dose levels using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
- Incidence of grade 3 and 4 treatment-related toxicitiesUp to 30 days after completion of study treatment
Grade 3 and 4 adverse events will be described and graded at all dose levels using the NCI CTCAE v5.0.