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

Plain English Summary

Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer is a Phase 1 clinical trial sponsored by City of Hope Medical Center studying Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8. This trial is testing a combination of two drugs, carfilzomib and sotorasib, to see if they are safe and effective for treating a specific type of advanced lung cancer. It is for patients with non-small cell lung cancer (NSCLC) that has spread and has a specific genetic mutation called KRAS G12C. Participants will receive the two drugs, undergo regular medical check-ups, and provide blood and tissue samples. Alternative treatments may include other targeted therapies or chemotherapy, depending on the patient's specific situation and prior treatments. The trial aims to enroll 15 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with advanced or metastatic non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. Patients must have previously been treated with a KRAS inhibitor and their cancer must be measurable. Individuals with certain heart conditions, active brain metastases, or uncontrolled infections may not be eligible. Participants must have adequate blood counts, liver, and kidney function, and be able to provide informed consent. This trial is studying Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine the highest safe dose of the drug combination and identify any serious side effects that occur during the first cycle of treatment. The specific primary outcome measures are: Incidence of dose limiting toxicities (During cycle 1 (each cycle is 28 days)); Incidence of grade 3 and 4 treatment-related toxicities (Up to 30 days after completion of study treatment). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with KRAS G12C-mutated non-small cell lung cancer, a group with limited effective options after initial therapies. This research targets Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This Phase I trial is an early step in evaluating a novel combination therapy for a specific lung cancer subtype, indicating potential for future targeted treatment development in a significant market Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of carfilzomib and sotorasib, and how this combination might fit with your previous treatments. Participation involves regular clinic visits for drug administration, physical exams, blood tests, and imaging scans. You will need to provide informed consent and agree to use effective birth control during and after the study if you are of childbearing potential. This trial is currently recruiting participants. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 15 participants

Interventions

• PROCEDURE: Biopsy — Undergo biopsy
• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• DRUG: Carfilzomib — Given IV
• PROCEDURE: Computed Tomography — Undergo CT
• PROCEDURE: Echocardiography — Undergo ECHO

Primary Outcomes

• Incidence of dose limiting toxicities (During cycle 1 (each cycle is 28 days))
• Incidence of grade 3 and 4 treatment-related toxicities (Up to 30 days after completion of study treatment)

Secondary Outcomes

• 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)

Full Eligibility Criteria

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
* 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 Criteria:

* 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)

Trial Locations

• City of Hope Medical Center, Duarte, California, United States
• City of Hope at Irvine Lennar, Irvine, California, United States

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Metastatic Cancer
• KRAS Mutation
• Oncology
• Targeted Therapy
• Chemotherapy
• Cancer Treatment
• Clinical Trials
• Drug Development

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