Sotorasib for Non-Small Cell Lung Cancer

Recruiting at 712 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Southwest Oncology Group

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back (recurrent) and has a specific mutation in the KRAS gene, known as KRAS G12C. Mutations in this gene may cause the cancer to grow. AMG 510, a targeted treatment against the KRAS G12C mutation, may help stop the growth of tumor cells.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received any systemic therapy, including chemotherapy or immunotherapy, within 21 days before joining the trial. Also, you cannot use strong inducers of CYP3A4 or CYP3A4 sensitive substrates within 14 days before and during the trial. It's best to discuss your current medications with the trial team.

What data supports the idea that Sotorasib for Non-Small Cell Lung Cancer is an effective drug?

The available research shows that Sotorasib is effective for treating non-small cell lung cancer with a specific mutation called KRAS G12C. It was granted accelerated approval by the US FDA for patients who have already tried other treatments. Studies have shown that Sotorasib has promising anticancer activity, especially in patients with this type of lung cancer. In clinical trials, patients experienced a significant response to the drug, meaning their cancer showed signs of shrinking or stopping growth. This makes Sotorasib a promising option for those who have not had success with other treatments. ^{1 2 3 4 5}

What safety data is available for Sotorasib in treating non-small cell lung cancer?

Sotorasib, also known as Lumakras, has been evaluated for safety in treating KRAS G12C-mutated non-small cell lung cancer (NSCLC). The FDA granted accelerated approval based on the CodeBreaK 100 trial, which showed an overall response rate of 36% in patients. Common adverse reactions (≥20%) included diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. Sotorasib has a manageable tolerability profile, with dose modifications allowed to manage toxicity. ^{1 3 4 5 6}

Is the drug Sotorasib a promising treatment for non-small cell lung cancer?

Yes, Sotorasib is a promising drug for non-small cell lung cancer. It has shown positive results in clinical trials, helping patients with a specific genetic mutation (KRAS G12C) in their cancer. It has been approved for use in the USA and Europe, offering new hope for patients who have already tried other treatments. ^{1 2 4 5 7}

Research Team

Sukhmani Padda, MD

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with advanced non-squamous non-small cell lung cancer that has a specific KRAS G12C mutation and has worsened after treatment. They must have had at least one systemic therapy, be able to swallow pills, not be pregnant or nursing, and agree to use contraception if applicable. People with certain heart conditions, other cancers, or those who can't take the study drug due to interactions are excluded.

Inclusion Criteria

Participants of reproductive potential must have a negative serum pregnancy test within 28 days prior to sub-study registration

My brain or spinal metastases have been treated and stable for at least a week.

My cancer can be measured on a CT or MRI scan taken within the last 28 days.

Exclusion Criteria

I haven't taken strong CYP3A4 inducers in the last 14 days and won't during the study.

I have a stomach or intestine condition that affects how medicines work in my body.

I haven't had radiation therapy in the last 14 days, except for brain metastases treatment which was over a week ago.

Treatment Details

Interventions

• Sotorasib (Targeted Therapy)

Trial Overview The trial is testing AMG 510 (Sotorasib), which targets the KRAS G12C mutation in stage IV or recurrent lung cancer. It's a phase II study aiming to see if this targeted treatment can stop tumor growth by focusing on this specific genetic change found in some tumors.

Participant Groups

Group I: Treatment (AMG 510) Experimental Treatment 1 Intervention

Patients receive AMG 510 PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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™) 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 (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]

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]

References

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

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

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

4. France pubmed.ncbi.nlm.nih.gov

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

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

Sotorasib: First Approval. [2022]

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

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

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

Sotorasib Edges Closer to Approval. [2021]