Sotorasib for Advanced Non-Small Cell Lung Cancer

(CodeBreaK201 Trial)

No longer recruiting at 91 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must not be taking: Proton-pump inhibitors, H2 antagonists

Disqualifiers: Small-cell lung cancer, Myocardial infarction, 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: Unknown

Duration: Up to 6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests sotorasib, a medication, to evaluate its effectiveness for people with advanced non-small cell lung cancer (NSCLC). Researchers aim to understand how the drug affects tumors in patients with the KRAS G12C gene mutation and low PD-L1 levels, markers that can influence cancer growth. Participants will receive either a high or low dose of sotorasib to compare effectiveness. This trial suits those with Stage IV NSCLC who have not received other treatments and have the KRAS G12C mutation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using proton-pump inhibitors (medications that reduce stomach acid), certain stomach acid reducers, and specific medications that affect liver enzymes. If you're taking any of these, you may need to stop or switch to a different medication.

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

Research has shown that sotorasib is generally safe for people. Studies have found that common side effects include diarrhea, muscle pain, nausea, tiredness, liver problems, and cough. More than 20% of patients in a study with 204 participants reported these side effects. Experts note that doctors can manage these risks and help control side effects if they occur.

Another study found that sotorasib provides lasting benefits for patients without introducing new safety concerns. While some side effects may occur, they are expected and typical for this kind of treatment. Overall, sotorasib has a well-understood safety profile, particularly for patients with advanced lung cancer that has a specific genetic change called the KRAS G12C mutation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for advanced non-small cell lung cancer (NSCLC) involve chemotherapy, immunotherapy, or targeted therapies that focus on specific genetic mutations. However, sotorasib is unique because it specifically targets the KRAS p.G12C mutation, which is a common driver of cancer growth in these patients. Unlike traditional options, sotorasib directly inhibits this mutation, potentially offering a more precise and effective treatment. Researchers are excited because this approach could lead to better outcomes for patients whose tumors are resistant to other treatments, especially those with low PD-L1 expression or an STK11 mutation. Additionally, the trial is exploring two dosing options, 960 mg and 240 mg daily, to determine the most effective and safest dosage for patients.

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

Research shows that sotorasib effectively treats non-small cell lung cancer (NSCLC) with a specific genetic change known as KRAS p.G12C. Studies have found that patients with this genetic change can experience significant tumor shrinkage when taking sotorasib. In this trial, participants will receive either 960 mg or 240 mg of sotorasib daily. In real-life use, patients on sotorasib lived longer on average than those receiving other treatments like docetaxel. Additionally, most patients tolerate sotorasib well without serious side effects. These findings suggest that sotorasib is a promising treatment option for people with KRAS p.G12C-mutated NSCLC. ^{3 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV NSCLC who have not been treated before, have a specific KRAS mutation (G12C), and either low PD-L1 levels or an STK11 co-mutation. They should be in good physical condition (ECOG score of 0 or 1) and cannot have had certain treatments within specified time frames.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is at stage IV and I haven't received treatment for this stage yet.

My cancer has a PD-L1 score under 1% or an STK11 mutation.

Exclusion Criteria

I have not had radiation therapy in the last 2 weeks.

I am not taking strong medications that affect liver enzymes or certain stomach acid drugs.

I have not had a heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotorasib at either 960 mg or 240 mg daily based on their tumor characteristics

Up to 6 years

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 tests two doses of Sotorasib (960 mg daily or 240 mg daily) to see how well it works on tumors with low PD-L1 levels (<1%) and/or STK11 co-mutations. The effectiveness will be measured by the change in tumor size according to RECIST criteria.

How Is the Trial Designed?

Group I: Sotorasib: 960 mg Daily Experimental Treatment 1 Intervention

Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express \< 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 960 mg daily. Participants will be stratified by known presence of STK11 mutation.

Group II: Sotorasib: 240 mg Daily Experimental Treatment 1 Intervention

Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express \< 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 240 mg daily. Participants will be stratified by known presence of STK11 mutation.

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?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

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]

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]

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 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 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 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]

Citations

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

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.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39601038/

Sotorasib for the treatment of locally advanced/metastatic ... Sotorasib is an oral targeted therapy option for the treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutations.

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

Sotorasib for Lung Cancers with KRAS p.G12C Mutation Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer ...

5. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(24)00494-X/fulltext

Real-world comparative effectiveness of sotorasib versus ... First study comparing real-world effectiveness of sotorasib vs. docetaxel treatment. Median OS was longer with sotorasib vs. docetaxel (2L HR=0.62; 2L+HR=0.65).

6. lumakrashcp.com lumakrashcp.com/sotorasib-safety

Safety & Adverse Reactions | LUMAKRAS® (sotorasib) The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough in CodeBreaK 100 (N=204).

7. academic.oup.com academic.oup.com/oncolo/article/30/1/oyae356/7976610

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 ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02967-2/fulltext

989P Sotorasib in advanced KRAS p.G12C-mutated non- ... 989P Sotorasib in advanced KRAS p.G12C-mutated non-small cell lung cancer (NSCLC): Safety and efficacy data from the global expanded access program (EAP)

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40542959/

Matching-Adjusted Indirect Comparison of Sotorasib ... In this MAIC, sotorasib and adagrasib showed comparable efficacy in previously treated advanced KRAS G12C-mutated NSCLC.