Sotorasib for Non-Small Cell Lung Cancer

Not currently recruiting at 723 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Southwest Oncology Group

Must not be taking: CYP3A4 inducers

Disqualifiers: Leptomeningeal disease, Cardiac disease, 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: 21 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of sotorasib for individuals with a specific type of advanced non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. The goal is to determine if this targeted treatment can halt cancer cell growth. Individuals with stage IV or recurrent non-squamous NSCLC with the KRAS G12C mutation, who have already tried other treatments, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

The trial does not specify if you need to stop taking your current medications, but you must not have received any systemic therapy within 21 days before joining. Additionally, you cannot use strong inducers of CYP3A4 or CYP3A4 sensitive substrates within 14 days before and during the trial.

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

Research has shown that sotorasib is generally safe for patients with advanced non-small cell lung cancer (NSCLC) who have a specific mutation called KRAS G12C. In previous studies, researchers controlled any major risks by adjusting the dose of sotorasib.

Real-world studies indicate that patients usually tolerate sotorasib well. Common side effects include diarrhea and other mild reactions, which are typically manageable. Overall, sotorasib appears to be a safe option for individuals with this type of lung cancer mutation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sotorasib is unique because it specifically targets a genetic mutation known as KRAS G12C, which is found in about 13% of non-small cell lung cancer cases. Most current treatments for this condition, like chemotherapy and immunotherapy, do not specifically target this mutation. Sotorasib works by inhibiting the abnormal signaling pathways driven by KRAS G12C, potentially leading to more effective and personalized treatment outcomes. Researchers are excited about sotorasib because it offers a targeted approach, providing new hope for patients with this previously hard-to-treat mutation.

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

Research has shown that sotorasib can help treat non-small cell lung cancer (NSCLC) with the KRAS G12C mutation. In studies, 41% of patients experienced tumor shrinkage or halted growth. On average, this improvement lasted about 12.3 months. Patients typically lived around 12.5 months after starting treatment, with the cancer not worsening for about 6.3 months. Compared to the usual treatment, docetaxel, sotorasib demonstrated longer overall survival. These findings suggest that sotorasib, which participants in this trial will receive, could be a promising option for people with this specific type of lung cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Sukhmani Padda, MD

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMG 510 orally once daily on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 3 years if the disease has not progressed, or every 6 months for 2 years if the disease has progressed.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Sotorasib

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.

How Is the Trial Designed?

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.

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?

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+

Published Research Related to This Trial

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 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 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]

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 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]

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

Molecular determinants of sotorasib clinical efficacy in ... We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRAS G12C -mutated NSCLC co-mutational subsets and transcriptional ...

4. 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).

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.22.02524

2-Year Analysis of CodeBreaK 100 Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 ...

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 ... A total of 456 adverse events were collected, among which diarrhea (n = 155), non-small cell lung cancer (n = 134), metastatic non-small cell ...

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

2-Year Analysis of CodeBreaK 100 Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 ...

9. 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 ...