What is the mechanism of action of this treatment?

Sotorasib is a KRAS G12C inhibitor that targets a specific mutation in the KRAS gene, halting cancer cell growth by inhibiting this mutation. Pembrolizumab is a PD-1 inhibitor that blocks the PD-1 pathway, enhancing the immune system's ability to attack cancer cells. These mechanisms are important for NSCLC patients as they allow for personalized treatment strategies based on the genetic and immune characteristics of their tumors, potentially improving treatment efficacy and patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for NSCLC, such as sotorasib and pembrolizumab, have distinct side effect profiles. Sotorasib, a KRAS G12C inhibitor, can cause diarrhea, nausea, liver enzyme elevations, and fatigue. Pembrolizumab, a PD-1 inhibitor, is associated with immune-related adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. When combined with platinum-based chemotherapy, additional side effects may include myelosuppression, nephrotoxicity, neurotoxicity, and gastrointestinal disturbances. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Small Cell Lung Cancer (NSCLC) that target specific genetic mutations and immune checkpoints. Sotorasib, a KRAS G12C inhibitor, has been approved for patients with advanced NSCLC harboring the KRAS G12C mutation. Pembrolizumab, a PD-1 inhibitor, has been approved for use in various settings, including as a monotherapy for patients with high PD-L1 expression and in combination with platinum-based chemotherapy for broader patient populations. Other similar FDA-approved treatments include nivolumab (another PD-1 inhibitor) and atezolizumab (a PD-L1 inhibitor), which are used in combination with chemotherapy for certain NSCLC patients.

What other types of research exist?

Promising novel alternatives for NSCLC treatment in 2024 include: 1) Nivolumab plus Ipilimumab combined with short-course chemotherapy, which has shown reduced rates of severe treatment-related adverse events (TRAEs) and limited chemotherapy administration. 2) Atezolizumab plus chemotherapy, which is investigational for squamous NSCLC and has shown potential benefits. These combinations represent emerging options that may offer improved efficacy and safety profiles for NSCLC patients.

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Checkpoint Inhibitor

Sotorasib Combo vs Pembrolizumab Combo for Advanced Lung Cancer

Phase 3

Recruiting

Research Sponsored by Amgen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

No history of systemic anticancer therapy in metastatic/non-curable settings

Histologically or cytologically confirmed diagnosis of nonsquamous stage IV or advanced Stage IIIB or IIIC NSCLC with KRAS p. G12C mutation and negative for PD-L1 expression by central testing or local laboratory testing confirmed through central testing

Must not have

Symptomatic (treated or untreated) brain metastases

Mixed histology NSCLC with either small-cell or large-cell neuroendocrine cell component or predominant squamous cell histology

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline up to eos (approximately 5.5 years)

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing two different drug combinations with chemotherapy to see which helps cancer patients live longer without their disease getting worse. One combination includes sotorasib, which targets cancer mutations, and the other includes pembrolizumab, which helps the immune system fight cancer. Pembrolizumab has been shown to improve overall survival in various cancers when combined with chemotherapy.

Who is the study for?

This trial is for adults with advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) that has a specific mutation (KRAS p. G12C) and no PD-L1 expression. They should not have had cancer treatment in the metastatic setting, be relatively fit (ECOG ≤ 1), and able to take oral medication.

What is being tested?

The study compares two treatments: Sotorasib with platinum chemotherapy versus Pembrolizumab with the same chemo, focusing on how long patients live without their cancer getting worse.

What are the potential side effects?

Possible side effects include liver problems, diarrhea, muscle pain from Sotorasib; immune reactions, fatigue, skin issues from Pembrolizumab; plus typical chemo-related nausea, hair loss.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I haven't had any systemic anticancer therapy for incurable cancer.

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My advanced lung cancer is KRAS G12C mutation positive and PD-L1 negative.

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I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have brain metastases that cause symptoms.

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My lung cancer is mixed type with specific cell features.

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I have been treated with a KRAS G12C inhibitor before.

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I haven't had a heart attack or unstable heart conditions in the last 6 months.

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My tumor has a specific genetic change that can be treated with approved medication.

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I cannot take pills due to a stomach or intestine problem.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline up to eos (approximately 5.5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline up to eos (approximately 5.5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline up to eos (approximately 5.5 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free Survival (PFS)

Secondary study objectives

Change in Summary Scores and Visual Analogue Scale (VAS) Scores

Disease Control

Duration of Response

+6 more

Side effects data

From 2022 Phase 1 trial • 20 Patients • NCT04887064

14%

Constipation

100%

80%

60%

40%

20%

Study treatment Arm

Normal Hepatic Function

Moderate Hepatic Impairment

Severe Hepatic Impairment

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Sotorasib combined with carboplatin and pemetrexedExperimental Treatment1 Intervention

Sotorasib administered in combination with carboplatin and pemetrexed.

Group II: Pembrolizumab combined with carboplatin and pemetrexedActive Control1 Intervention

Pembrolizumab administered in combination with carboplatin and pemetrexed.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sotorasib

2021

Completed Phase 1

~370

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Sotorasib is a KRAS G12C inhibitor that targets a specific mutation in the KRAS gene, halting cancer cell growth by inhibiting this mutation. Pembrolizumab is a PD-1 inhibitor that blocks the PD-1 pathway, enhancing the immune system's ability to attack cancer cells. These mechanisms are important for NSCLC patients as they allow for personalized treatment strategies based on the genetic and immune characteristics of their tumors, potentially improving treatment efficacy and patient outcomes.

The impact of smoking status on the progression-free survival of non-small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta-analysis.Emerging therapeutic agents for lung cancer.