Sotorasib for Lung Cancer

Recruiting at 8 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests sotorasib (also known as Lumakras or AMG-510) to determine its safety and effectiveness for individuals with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called KRAS G12C. The study targets those who have not received treatment since their cancer became advanced. It suits individuals aware of this specific mutation who have opted against initial chemotherapy or immunotherapy. Participants will take sotorasib daily and undergo tumor biopsies to help researchers understand the drug's effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that sotorasib is generally well-tolerated by patients with advanced non-small cell lung cancer (NSCLC) who have the KRAS G12C mutation. In studies, patients experienced side effects, but dose adjustments usually managed these effectively.

Another study found that sotorasib is safe for use in everyday settings for similar patients, indicating that people outside of clinical trials also tolerated it well. Importantly, continued use of the drug has not revealed any new safety concerns.

Overall, sotorasib has a clear safety profile, and past studies have effectively managed key risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Sotorasib is unique because it specifically targets a mutation in the KRAS gene, which is a common driver of lung cancer. Unlike traditional chemotherapy that affects both cancerous and healthy cells, sotorasib focuses on this mutation, potentially reducing side effects and improving effectiveness. Researchers are excited because targeting KRAS has been a challenge for decades, and sotorasib represents a breakthrough in achieving this goal.

What evidence suggests that sotorasib might be an effective treatment for advanced non-small cell lung cancer?

Research has shown that sotorasib, the treatment under study in this trial, can help treat advanced non-small cell lung cancer (NSCLC) with a specific change in the KRAS gene, known as the G12C mutation. In previous studies, patients lived without their cancer worsening for an average of 6.8 months and lived for an average of 12.5 months overall. Many patients experienced tumor shrinkage and maintained disease control for a significant time. Real-world evidence also supports its effectiveness and safety in advanced cases of this type of lung cancer. Overall, sotorasib appears promising for individuals with this specific gene change in their cancer. ^{2 4 5 6 7}

Who Is on the Research Team?

Gregory Riely, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer

Are You a Good Fit for This Trial?

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 willing to have tumor biopsies before and during treatment.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000826

Real-world effectiveness and tolerability of sotorasib in ... Sotorasib has shown efficacy in a phase 3 trial compared to docetaxel among previously treated non-small cell lung cancer (NSCLC) patients with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39970524/

Real-world effectiveness and tolerability of sotorasib in ... This study gave insights into effectiveness and safety of sotorasib in a real-world setting, in advanced or metastatic KRAS G12C-mutated non-squamous NSCLC.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2103695

Sotorasib for Lung Cancers with KRAS p.G12C Mutation The median progression-free survival was 6.8 months, and the median overall survival was 12.5 months. In addition, tumor shrinkage and disease control were ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02524

2-Year Analysis of CodeBreaK 100 These results demonstrate the long-term benefit of sotorasib, including in subgroups with poor prognosis. Introduction. Overall survival (OS) ...

5. nature.com nature.com/articles/s41591-025-03732-5

Molecular determinants of sotorasib clinical efficacy in ... Molecular determinants of KRAS(G12C)inhibitor efficacy in KRASG12C-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39846981/

Pooled safety analysis and management of sotorasib-related ... Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12566659/

Sex-Related Safety Signals of Sotorasib in Non-Small Cell ... Background: Sotorasib, a KRAS G12C inhibitor, is approved for treating non-small cell lung cancer (NSCLC) and has shown a distinct safety ...