Sotorasib for Lung Cancer

Recruiting at 7 trial locations

Overseen By Gregory Riely, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4 inducers, P-gp substrates

Disqualifiers: Symptomatic brain metastases, Congestive heart failure, Hepatitis B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 months

39 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to see if sotorasib is a safe and effective treatment for people with advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation who have not received treatment for their cancer since it became advanced. (Participants have not received a "first-line therapy" since their cancer became advanced.)

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications that affect liver enzymes (CYP3A4 and P-gp substrates) within 14 days before starting the trial unless approved by the principal investigator.

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

Sotorasib has shown promising results in treating non-small cell lung cancer (NSCLC) with a specific KRAS mutation, known as KRAS G12C. In clinical trials, it has demonstrated the ability to shrink tumors in a significant number of patients and has been approved for use in those who have already tried other treatments. ^{1 2 3 4 5}

How is the drug Sotorasib unique for treating lung cancer?

Sotorasib is unique because it is the first drug specifically designed to target and inhibit the KRAS G12C mutation, which is a common mutation in non-small cell lung cancer. It works by blocking the signals that promote cancer cell growth, offering a new option for patients who have already tried other treatments. ^{1 2 3 4 5}

Research Team

Gregory Riely, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer

Eligibility Criteria

This trial is for individuals with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called KRAS G12C. Participants should not have received any first-line therapy since their cancer became advanced.

Inclusion Criteria

I agree to use condoms with spermicide if I'm sexually active.

I am able to care for myself but may not be able to do active work.

I am not able to have children or I am using effective birth control.

Exclusion Criteria

I do not have any active or chronic liver diseases.

Positive hepatitis B (HBV) surface antigen (HBsAg) or positive hepatitis C antibody (anti-HCV)

Currently enrolled in another investigational device or drug study, or less than 28 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pretreatment

Pretreatment tumor biopsy is completed before starting sotorasib

1 week

Treatment

Participants receive sotorasib 960 mg daily

6 months

CT scans every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sotorasib

Trial Overview The study is testing the safety and effectiveness of a drug named Sotorasib in treating NSCLC with the KRAS G12C mutation. It aims to understand if this drug can be an effective treatment option.

Participant Groups

Group I: Sotorasib Experimental Treatment 1 Intervention

All patients will start at sotorasib 960 mg (8 pills) daily within 7 days of completion of the pretreatment tumor biopsy.

Sotorasib is already approved in United States, European Union for the following indications:

Approved in United States as Lumakras for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Approved in European Union as Lumakras for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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 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 the phase II CodeBreak 100 trial, the KRASG12C inhibitor sotorasib showed promising efficacy, with over one-third of patients with non-small cell lung cancer responding to the treatment.

Patients treated with sotorasib experienced a median progression-free survival of nearly 7 months, supporting its potential as a significant therapeutic option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib Edges Closer to Approval. [2021]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Sotorasib Edges Closer to Approval. [2021]

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

Sotorasib: First Approval. [2022]

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

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