Carfilzomib + Sotorasib for Lung Cancer

Recruiting at 1 trial location

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination Carfilzomib and Sotorasib for lung cancer?

Sotorasib has shown promising anticancer activity in patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC), with a clinically relevant response rate and duration observed in clinical trials. It is approved for use in patients with this specific mutation who have been previously treated, indicating its effectiveness in this context. ^{1 2 3 4 5}

Is the combination of Carfilzomib and Sotorasib safe for humans?

Sotorasib, also known as Lumakras, has been approved for use in certain lung cancer patients and has a manageable safety profile, with common side effects including diarrhea, muscle pain, nausea, fatigue, liver issues, and cough. However, specific safety data for the combination of Carfilzomib and Sotorasib is not available in the provided research. ^{2 3 4 5 6}

What makes the drug combination of Carfilzomib and Sotorasib unique for lung cancer treatment?

This drug combination is unique because it includes Sotorasib, the first approved drug specifically targeting the KRAS G12C mutation found in some lung cancers, offering a new option for patients with this specific genetic mutation. ^{1 2 3 5 7}

Research Team

Jyoti Malhotra, MD

Principal Investigator

City of Hope Medical Center

Ravi Salgia

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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 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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sotorasib: First Approval. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. France pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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