What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) similar to Adagrasib, a KRAS G12C inhibitor, include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as those for EGFR or ALK mutations, often cause skin rashes, diarrhea, and liver enzyme abnormalities. Immunotherapies, like PD-1/PD-L1 inhibitors, can lead to immune-related adverse events including pneumonitis, colitis, hepatitis, and endocrinopathies. Chemotherapy regimens, such as those involving platinum-based drugs, frequently result in nausea, vomiting, fatigue, and myelosuppression. These side effects vary in severity and frequency among patients.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). For instance, selpercatinib and pralsetinib are approved for RET fusion-positive NSCLC, and osimertinib is approved for EGFR-mutant NSCLC. Specifically related to KRAS G12C mutations, the trial of Adagrasib in combination with pembrolizumab is being studied, highlighting the ongoing efforts to target this mutation. These approvals and ongoing studies reflect the advancements in personalized, genotype-directed therapies for NSCLC.

What other types of research exist?

Promising alternatives to Adagrasib for NSCLC patients with KRAS G12C mutation include: 1. Larotrectinib and Entrectinib for patients with NTRK gene fusions. 2. Afatinib, Dacomitinib, and Osimertinib for patients with EGFR uncommon alterations such as G719A, S768I, and L861Q. 3. Gefitinib plus Simvastatin for patients with wild-type EGFR nonadenocarcinomas. These alternatives have shown efficacy in clinical trials and may be considered based on the specific genetic profile of the tumor.

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Small Molecule Drug

Adagrasib + Pembrolizumab for Lung Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as Adagrasib, specifically inhibit the KRAS G12C mutation, which is a common driver mutation in NSCLC. By blocking the KRAS G12C protein, these inhibitors prevent cancer cell proliferation and survival. Immunotherapies, like pembrolizumab, enhance the immune system's ability to recognize and destroy cancer cells by targeting PD-1/PD-L1 pathways. Chemotherapy, using agents like cisplatin and pemetrexed, works by killing rapidly dividing cells, including cancer cells. Understanding these mechanisms is crucial for NSCLC patients as it helps in selecting the most effective treatment based on their specific genetic mutations and overall health condition.

Phase 2 & 3

Recruiting

Research Sponsored by Mirati Therapeutics Inc.

Eligibility Criteria Checklist

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

Must have

Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS

Phase 3: Histologically confirmed diagnosis of unresectable or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50%

Must not have

Phase 2 and Phase 3: Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation (e.g., AMG 510)

Phase 2: Active brain metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 36 months

Awards & highlights

Summary

This trial tests two drugs, MRTX849 and pembrolizumab, in patients with advanced lung cancer who have a specific genetic mutation. MRTX849 targets the mutation to stop cancer growth, while pembrolizumab boosts the immune system to fight the cancer. The study aims to see how well these treatments work alone and together.

Who is the study for?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called KRAS G12C. Participants must have measurable disease and no prior treatments for metastatic NSCLC. Those with certain brain metastases can join if they don't require immediate treatment.

What is being tested?

The study tests MRTX849 alone and combined with Pembrolizumab in Phase 2, while Phase 3 compares Adagrasib plus Pembrolizumab against only Pembrolizumab in patients whose tumors show high levels of a protein called PD-L1.

What are the potential side effects?

Possible side effects include fatigue, nausea, diarrhea, skin rash, liver enzyme changes, and potential immune-related issues such as inflammation of organs or infusion reactions.

Eligibility Criteria

Inclusion Criteria

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

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My NSCLC is inoperable or has spread, with a KRAS G12C mutation.

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My NSCLC is inoperable or has spread, with a KRAS G12C mutation and high PD-L1 levels.

Exclusion Criteria

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

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I have had treatments like chemotherapy or immunotherapy for advanced lung cancer.

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I have active cancer spread to my brain.

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I have not received lung radiation over 30 Gy in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 36 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase 2: To evaluate the efficacy of Adagrasib monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC.

Phase 3: To compare efficacy of Adagrasib in combination with pembrolizumab versus pembrolizumab

Secondary study objectives

Phase 2: Duration of Response

Phase 2: Progression Free Survival

Phase 2: To characterize the safety and tolerability of study treatments in selected populations

+8 more

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Phase 3 Cohort 3 Investigational ArmExperimental Treatment1 Intervention

Adagrasib BID in combination with pembrolizumab

Group II: Phase 2 Cohort 2: PD-L1 TPS ≥1%Experimental Treatment1 Intervention

Cohort 2: Adagrasib BID in combination with pembrolizumab

Group III: Phase 2 Cohort 1b: PD-L1 TPS <1%Experimental Treatment1 Intervention

Cohort 1b: Adagrasib BID monotherapy

Group IV: Phase 2 Cohort 1a: PD-L1 TPS <1%Experimental Treatment1 Intervention

Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab

Group V: Phase 3 Cohort 4 Comparator ArmActive Control1 Intervention

Pembrolizumab

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Adagrasib

2023

Completed Phase 1

~20

0 / 5Eligibility 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

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as Adagrasib, specifically inhibit the KRAS G12C mutation, which is a common driver mutation in NSCLC. By blocking the KRAS G12C protein, these inhibitors prevent cancer cell proliferation and survival. Immunotherapies, like pembrolizumab, enhance the immune system's ability to recognize and destroy cancer cells by targeting PD-1/PD-L1 pathways. Chemotherapy, using agents like cisplatin and pemetrexed, works by killing rapidly dividing cells, including cancer cells. Understanding these mechanisms is crucial for NSCLC patients as it helps in selecting the most effective treatment based on their specific genetic mutations and overall health condition.