Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer

NCT06249282 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23477NCI-2023-11093P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Advanced Lung Non-Small Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities

  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.

  During cycle 1 (each cycle is 28 days)

• Incidence of grade 3 and 4 treatment-related toxicities

  Grade 3 and 4 adverse events will be described and graded at all dose levels using the NCI CTCAE v5.0.

  Up to 30 days after completion of study treatment

Secondary Outcomes (4)

• Objective response rate

  From the start of treatment until disease progression/recurrence, assessed up to 30 days after completion of study treatment

• Duration of response

  From treatment response to progression or death, assessed up to 30 days after completion of study treatment

• Progression-free survival

  From day 1 of treatment until the criteria for disease progression is met or until death, assessed up to 30 days after completion of study treatment

• Overall survival

  From the date of study enrollment to the date of death, assessed up to 30 days after completion of study treatment

Study Arms (1)

Treatment (carfilzomib, sotorasib)

EXPERIMENTAL

Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 of each cycle and sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO at screening and undergo CT or MRI and collection of blood samples at screening and on study. Patients may undergo optional biopsies on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Carfilzomib; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Magnetic Resonance Imaging; Drug: Sotorasib

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (carfilzomib, sotorasib)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (carfilzomib, sotorasib)

Carfilzomib DRUG

Given IV

Also known as: Carfilnat, CFZ, Kyprolis, PR-171

Treatment (carfilzomib, sotorasib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (carfilzomib, sotorasib)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (carfilzomib, sotorasib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (carfilzomib, sotorasib)

Sotorasib DRUG

Given PO

Also known as: AMG 510, AMG-510, AMG510, Lumakras, Lumykras

Treatment (carfilzomib, sotorasib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Biopsy; Specimen Handling; carfilzomib; Magnetic Resonance Spectroscopy; sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Ravi Salgia, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Jyoti Malhotra, MD (Co-PI)

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: February 8, 2024
• Study Start: April 24, 2024
• Primary Completion: March 19, 2026
• Study Completion: March 19, 2026
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

US (2)