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Advanced Lung Non-Small Cell CarcinomaPhase 1NCT06249282

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

A Phase 1 study testing Biopsy, Biospecimen Collection and Carfilzomib in people with Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by City of Hope Medical Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Carfilzomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
24 Apr 2024to 24 Nov 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites, 2 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Ravi Salgia, 626-359-8111, rsalgia@coh.org

    Ravi Salgia, MD

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Ravi Salgia, 626-359-8111, rsalgia@coh.org

    Ravi Salgia, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase I Clinical Trial of Carfilzomib in Combination With Sotorasib in Patients With KRASG12C Mutated Advanced Non-Small Cell Lung Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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, including progression-free survival (PFS), duration of response (DOR), and overall survival (OS) at the recommended dose level.

EXPLORATORY OBJECTIVES:

  1. Evaluate the pharmacokinetics of the combination of carfilzomib and sotorasib.

II. Explore biomarkers of response and resistance through tumor biopsies and circulating tumor deoxyribonucleic acid (ctDNA).

OUTLINE: This is a dose-escalation study of carfilzomib in combination with (fixed-dose) sotorasib.

Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16 of each cycle and sotorasib orally (PO) once daily (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 echocardiography (ECHO) at screening and undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples at screening and on study. Patients may undergo optional biopsies on study.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Biopsy, Biospecimen Collection, Carfilzomib, Computed Tomography, Echocardiography
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • CarfilzomibDrug

    Also called Carfilnat, CFZ, Kyprolis, PR-171

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • SotorasibDrug

    Also called AMG 510, AMG-510, AMG510, Lumakras

    Given PO

Study groups in NCT06249282
Study groupRoleWhat they receive
Treatment (carfilzomib, sotorasib)ExperimentalPatients 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.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Carfilzomib; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Magnetic Resonance Imaging; Drug: Sotorasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: During cycle 1 (each cycle is 28 days)

  2. 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.

    Measured: Up to 30 days after completion of study treatment

Secondary outcomes (4)

  1. Objective response rate

    Defined as the proportion of all subjects with confirmed partial response or complete response, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Response rate will be summarized by frequencies and percentages, along with the corresponding exact 95% confidence intervals.

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

  2. Duration of response

    Will be estimated using the Kaplan-Meier method.

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

  3. Progression-free survival

    Disease progression will be defined using RECIST version 1.1. Will be estimated using the Kaplan-Meier method.

    Measured: 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

  4. Overall survival

    Will be estimated using the Kaplan-Meier method.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2024
  2. Study start24 Apr 2024
  3. Primary completion24 Nov 2026 (estimated)
  4. Study completion24 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06249282
Sponsor's protocol ID
23477
Other IDs
NCI-2023-11093, 23477, P30CA033572
Status last verified
Apr 2026
First submitted
11 Jan 2024
Last updated
3 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Biospecimen Collection and Carfilzomib in people with Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by City of Hope Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities (time frame: During cycle 1 (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06249282.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2026.

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