Carfilzomib + Sotorasib for Lung Cancer

Recruiting at 1 trial location

Overseen By Ravi Salgia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Chemotherapy, Immunotherapy, KRAS inhibitors, others

Disqualifiers: Uncontrolled illness, Chronic hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 28 days per cycle, repeated until disease progression or unacceptable toxicity

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, carfilzomib and sotorasib, to determine their safety and effectiveness in treating KRAS G12C-mutated non-small cell lung cancer (NSCLC) that has spread. Carfilzomib stops cancer cells from eliminating damaged proteins, which can slow tumor growth and kill cancer cells. Sotorasib targets a common mutation in some lung cancer cells to inhibit their growth. This trial may suit individuals with advanced or metastatic NSCLC with the KRAS G12C mutation who have not responded to prior KRAS inhibitor treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop chemotherapy, immunotherapy, radiation therapy, KRAS inhibitors, and investigational therapies for a certain period before starting the trial. However, the protocol does not specify about other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

A previous study found the combination of carfilzomib and sotorasib to be generally safe. Researchers observed 98 patients and noted some side effects, which were mostly manageable. Another study reported that about 64.7% of patients experienced treatment-related side effects, with some being more serious. However, these side effects resembled those seen in other studies.

Both carfilzomib and sotorasib have undergone individual testing and can be safe with careful monitoring. This trial is in its early stages, primarily aiming to determine the safest way to use this combination and identify any potential side effects. Although data on this specific combination is limited, the individual drugs have demonstrated safe use with proper monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about carfilzomib and sotorasib for lung cancer because they offer a fresh approach compared to standard treatments. Carfilzomib is a proteasome inhibitor, which means it disrupts the protein degradation process in cancer cells, leading to their death. Sotorasib, on the other hand, targets a specific mutation in the KRAS gene, which is a common driver of cancer proliferation. This targeted action could provide a more effective and potentially less toxic option for patients with this mutation, setting it apart from conventional chemotherapy regimens that broadly attack rapidly dividing cells.

What evidence suggests that this trial's treatments could be effective for advanced or metastatic NSCLC?

Research has shown that sotorasib, a drug targeting the KRAS G12C mutation, improves response rates and increases survival in patients with non-small cell lung cancer (NSCLC) compared to standard treatments. Approximately 25% of patients treated with sotorasib survived two years after starting treatment. Carfilzomib blocks a protein that breaks down damaged proteins, helping to stop tumor growth and kill cancer cells. In this trial, participants will receive a combination of carfilzomib and sotorasib, believed to enhance treatment effectiveness by attacking the cancer in different ways. Both drugs have shown promise, suggesting they could form a powerful combination for fighting advanced or metastatic NSCLC with the KRAS G12C mutation. ^{2 6 7 8 9}

Who Is on the Research Team?

Jyoti Malhotra, MD

Principal Investigator

City of Hope Medical Center

Ravi Salgia

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic non-small cell lung cancer that has a specific mutation called KRAS G12C. Participants should have measurable disease and may have had prior treatments, but there are certain criteria they must meet to join.

Inclusion Criteria

Hemoglobin (Hb) ≥ 9 g/dL

Measurable disease by RECIST v1.1

Agreement to use effective birth control or abstain from heterosexual activity

Exclusion Criteria

I have HIV with a detectable viral load.

Pregnant or breastfeeding (females only)

I am currently taking antibiotics for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive carfilzomib IV and sotorasib PO in 28-day cycles

28 days per cycle, repeated until disease progression or unacceptable toxicity

6 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Optional Biopsy

Participants may undergo optional biopsies on study

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Sotorasib

Trial Overview The trial is testing the combination of two drugs, Carfilzomib and Sotorasib, to see if they're safe together, what the best dose might be, and how well they work against this type of lung cancer. It includes tests like CT scans, MRIs, biopsies, and heart checks.

How Is the Trial Designed?

Group I: Treatment (carfilzomib, sotorasib) Experimental Treatment 7 Interventions

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.

Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Sotorasib (LUMAKRAS™) is an innovative treatment specifically targeting KRAS G12C mutations in solid tumors, particularly effective for non-small cell lung cancer (NSCLC) and colorectal cancer.

In May 2021, sotorasib received accelerated approval from the US FDA for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have undergone at least one prior treatment, marking a significant milestone in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: First Approval. Blair, HA.[2022]

Sotorasib is an irreversible small molecule inhibitor specifically targeting the KRAS G12C mutation, which is found in 13% of lung adenocarcinomas, and has shown significant tumor regression in preclinical studies and clinical trials.

In a reported case, a patient with metastatic KRAS G12C-mutated NSCLC responded remarkably well to sotorasib as a first-line therapy, suggesting its potential as an effective initial treatment option for this type of cancer, particularly in patients with additional health challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib as First-Line Treatment for Advanced KRAS G12C-Mutated Non-Small Cell Lung Carcinoma: A Case Report. Iska, S., Alley, EW.[2023]

Sotorasib and adagrasib, both KRAS G12C-targeting agents, have shown promising efficacy in treating non-small cell lung cancer (NSCLC), with sotorasib achieving an overall response rate of 41% and a progression-free survival of 6.3 months, while adagrasib had an overall response rate of 42.9% and a progression-free survival of 6.5 months.

Both drugs have received accelerated FDA approval and are now recommended as second-line treatment options for patients with KRAS G12C-mutated NSCLC, although they come with common side effects like diarrhea and fatigue, highlighting the need for further studies to refine their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. Mausey, N., Halford, Z.[2023]

Sotorasib (Lumakras) received accelerated FDA approval for treating advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, showing an overall response rate of 36% in a study of 124 patients.

The median duration of response to sotorasib was 10 months, with common side effects including diarrhea, musculoskeletal pain, and nausea, highlighting its efficacy and safety profile as a targeted therapy for this specific cancer mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. Nakajima, EC., Drezner, N., Li, X., et al.[2022]

Sotorasib is a first-in-class oral medication that specifically targets the KRAS G12C mutation in non-small cell lung cancer (NSCLC), showing a clinically relevant objective response rate in patients during the CodeBreaK 100 trial.

The drug has a manageable safety profile, allowing for dose adjustments to handle any side effects, making it a valuable treatment option for patients with advanced KRAS G12C mutation-positive NSCLC who have already undergone other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. Lee, A.[2022]

In a phase 2 trial involving 126 patients with KRAS p.G12C-mutated advanced non-small-cell lung cancer (NSCLC), sotorasib demonstrated a 37.1% objective response rate, including complete responses in 3.2% of patients, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 12.5 months and a median progression-free survival of 6.8 months, with manageable safety profiles, as 69.8% of patients experienced treatment-related adverse events, mostly of grade 3 severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. Skoulidis, F., Li, BT., Dy, GK., et al.[2022]

Sotorasib is the first commercially available KRASG12C inhibitor, showing promise in improving outcomes for patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), which is prevalent among smokers.

Despite its potential, there are ongoing questions about sotorasib's effectiveness in the brain, optimal dosing, and how it compares to standard treatments, highlighting the need for further research on resistance mechanisms and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. Strohbehn, GW., Sankar, K., Qin, A., et al.[2022]

Citations

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Spotlight on Sotorasib (AMG 510) for KRASG12C Positive ... Based on promising results in both preclinical and clinical trials, sotorasib, a novel KRAS G12C inhibitor, was given conditional approval by the FDA in May ...

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An updated overview of K-RAS G12C inhibitors in advanced ... Clinical trials have shown that KRAS G12C inhibitors improved objective response rates and progression-free survival compared with standard treatments. These ...

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P3.12E.04 Long-Term Outcomes with Sotorasib in KRAS ... Approximately a quarter of patients were still alive after 2 years. Efficacy was demon- strated across subgroups including those with poorer prognostic in-.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825003130

KRAS mutations in non-small cell lung cancer Similarly, adagrasib has demonstrated improved outcomes, with a 45 % response rate in patients with NSCLC during early-phase clinical trials (Awad et al., 2021) ...

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KRAS G12C inhibitor combination therapies This review article summarizes the latest evidence from the clinical trials of KRAS G12C inhibitor combinations and discusses other possible combinations with ...

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Amgen Showcases Oncology Pipeline At ASCO 2020 Notable data from the oncology pipeline include updated first-in-human studies evaluating sotorasib (AMG 510), a first-in-class investigational ...

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EP.12H.07 A Phase I Clinical Trial of Carfilzomib in ... Real-world efficacy and safety data of ALK TKIs were collected in the same cross-section. The primary endpoint is real-world progression-free survival (rwPFS) ...