What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve targeted therapies that inhibit specific molecular pathways critical for tumor growth and survival. For instance, KRAS G12C inhibitors like adagrasib (MRTX849) specifically target the KRAS G12C mutation, which is a common driver in NSCLC, by irreversibly binding to the mutant KRAS protein and inhibiting its activity. Similarly, therapies targeting the broader KRAS-MAPK pathway, such as those being studied in the MRTX0902 trial, aim to disrupt the signaling cascade that promotes cancer cell proliferation and survival. These targeted treatments are crucial for NSCLC patients as they offer a more personalized approach, potentially leading to better efficacy and fewer side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) targeting the KRAS-MAPK pathway and KRAS G12C mutations, such as MRTX0902 and MRTX849 (adagrasib), often have side effects including diarrhea, nausea, fatigue, and liver enzyme abnormalities. Other KRAS G12C inhibitors like sotorasib may also cause similar adverse effects. Additionally, targeted therapies in NSCLC can lead to skin rash, stomatitis, and gastrointestinal issues. Chemotherapy regimens, often used in combination with targeted therapies, typically result in myelosuppression, increased risk of infection, neuropathy, and gastrointestinal disturbances.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Non-Small Cell Lung Cancer (NSCLC) with specific genetic mutations. For patients with KRAS G12C mutations, sotorasib and adagrasib have been approved as targeted therapies. These drugs specifically inhibit the KRAS G12C mutation, offering a personalized treatment approach. Additionally, MEK inhibitors may be considered for tumors with other KRAS alterations after standard treatments have been exhausted. These approvals highlight the advancements in personalized medicine for NSCLC, focusing on genetic mutations within the KRAS-MAPK pathway.

What other types of research exist?

Promising novel alternatives for NSCLC patients targeting the KRAS-MAPK pathway and KRAS G12C mutations include: 1) Sotorasib (AMG 510), another KRAS G12C inhibitor that has shown efficacy in clinical trials. 2) Selpercatinib and pralsetinib, which are RET inhibitors, may be considered for patients with RET mutations. 3) Antiangiogenic multikinase inhibitors like cabozantinib and vandetanib, which have shown improvements in progression-free survival. 4) Immunotherapy options such as immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) which have become standard treatments for various mutations in NSCLC.

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MAPK Pathway Inhibitor

MRTX0902 + MRTX849 for Solid Tumors

Phase 1 & 2

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

Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study

Unresectable or metastatic disease

Must not have

History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow oral medications

Major surgery within 4 weeks of first dose of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, MRTX0902, alone and with another drug, adagrasib, in patients with advanced cancers that have specific genetic mutations. The goal is to see if these drugs are safe and can effectively block cancer growth signals. Adagrasib has shown promising results in treating certain types of advanced cancers.

Who is the study for?

This trial is for adults with advanced solid tumors that have specific mutations in the KRAS-MAPK pathway, who can't be cured by other treatments or choose not to undergo them. Participants must have a tumor that can be biopsied, measurable disease, good organ function, and an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory).

What is being tested?

The study tests MRTX0902 alone and combined with MRTX849 (adagrasib) on patients with certain genetic changes in their tumors. It's an early-stage trial to check how safe these drugs are, how the body processes them, and if they work against cancer.

What are the potential side effects?

Possible side effects include typical reactions from cancer medications such as nausea, fatigue, diarrhea; however specific side effects will depend on patient response to MRTX0902 and adagrasib which target mutations within cancer cells.

Eligibility Criteria

Inclusion Criteria

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

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My tumor can be biopsied for study purposes.

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My cancer cannot be removed by surgery or has spread to other parts of my body.

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I have no curative treatment options left or available to me.

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My cancer was confirmed through testing and has specific genetic changes.

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I am fully active or have some restrictions but can still care for myself.

Exclusion Criteria

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

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I have a history of serious gut issues that could affect medication absorption.

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I have not had major surgery in the last 4 weeks.

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I have had pneumonitis or lung disease affecting the tissue and space around the air sacs.

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I have heart problems.

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I have active brain metastases or carcinomatous meningitis.

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I have been treated with a specific inhibitor before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 days for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Apparent total plasma clearance when dosed orally

Apparent volume of distribution when dosed orally

Area under the plasma concentration versus time curve

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 2Experimental Treatment2 Interventions

MRTX0902 and adagrasib combination RP2D administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12C mutation to include the following: NSCLC, CRC, Other Solid Tumors

Group II: Phase 1/1B MonotherapyExperimental Treatment1 Intervention

Dose Escalation/Evaluation

Group III: Phase 1/1B Combination TherapyExperimental Treatment2 Interventions

Dose Escalation/Evaluation and Food Effect Assessment

0 / 11Eligibility 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) often involve targeted therapies that inhibit specific molecular pathways critical for tumor growth and survival. For instance, KRAS G12C inhibitors like adagrasib (MRTX849) specifically target the KRAS G12C mutation, which is a common driver in NSCLC, by irreversibly binding to the mutant KRAS protein and inhibiting its activity. Similarly, therapies targeting the broader KRAS-MAPK pathway, such as those being studied in the MRTX0902 trial, aim to disrupt the signaling cascade that promotes cancer cell proliferation and survival. These targeted treatments are crucial for NSCLC patients as they offer a more personalized approach, potentially leading to better efficacy and fewer side effects compared to traditional chemotherapy.