What side effects are associated with this type of intervention?

Common side effects of targeted cancer therapies, including KRAS inhibitors like MRTX849 (adagrasib), often include gastrointestinal issues such as diarrhea and nausea, skin problems like rash and dry skin, and fatigue. Other potential side effects can include liver enzyme abnormalities and hypertension. These side effects are typically manageable but can vary in severity.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for cancer treatment, particularly those focusing on specific genetic mutations and pathways. For instance, osimertinib targets EGFR mutations in non-small cell lung cancer, and vemurafenib targets BRAF V600E mutations in melanoma. While specific KRAS G12C inhibitors like adagrasib (MRTX849) are still under investigation, the FDA has approved sotorasib, another KRAS G12C inhibitor, for the treatment of non-small cell lung cancer with this mutation. These approvals highlight the ongoing advancements in precision oncology, aiming to tailor treatments based on individual genetic profiles.

What other types of research exist?

Promising alternatives to MRTX849 (adagrasib) for cancer patients include regorafenib, a multikinase inhibitor showing efficacy in various sarcomas and gastrointestinal stromal tumors, and temsirolimus, an mTOR inhibitor with potential benefits in endometrial cancer and other malignancies. Venetoclax combined with low-dose cytarabine is also a novel option for acute myeloid leukemia.

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Small Molecule Drug

MRTX849 for Cancer

Verified Trial

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

Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation

Unresectable or metastatic disease

Must not have

History of intestinal disease or major gastric surgery or inability to swallow oral medications

Other active cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 20 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new pill called MRTX849 (adagrasib) for patients with advanced cancers that have a specific genetic change called KRAS G12C. The pill aims to block this change and stop the cancer from growing. Adagrasib is similar to another approved treatment and is intended for patients with this genetic change who have already received other treatments.

Who is the study for?

This trial is for adults with advanced solid tumors that have a specific mutation called KRAS G12C. They should have tried all standard treatments without success or declined them, and their cancer must be inoperable or spread to other parts of the body. People can't join if they have another active cancer, serious gut diseases, major stomach surgery history, trouble swallowing pills, or HER2 positive breast cancer.

What is being tested?

The study tests MRTX849 (adagrasib) to see how safe it is and how well patients tolerate it. It also looks at what the drug does inside the body and whether it works against cancers with the KRAS G12C mutation. Patients may also receive other drugs like Pembrolizumab, Afatinib, or Cetuximab as part of their treatment.

What are the potential side effects?

Possible side effects from these medications include fatigue, skin reactions, diarrhea and other digestive issues; liver problems; allergic reactions; lung inflammation; changes in blood cell counts leading to increased infection risk or bleeding problems.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has a KRAS G12C mutation.

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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 NSCLC and either there's no standard treatment available or I've declined it.

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I have been diagnosed with HER2 positive breast cancer.

Exclusion Criteria

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

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I have had major stomach surgery or can't swallow pills.

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I do not have any other active cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 20 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~20 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 20 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

Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation

Evaluate clinical activity/efficacy of MRTX849

Evaluate the pharmacokinetics of MRTX849

Secondary study objectives

Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents

Establish maximum tolerated dose

Evaluate the pharmacokinetics of MRTX849 administered with food

+1 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

9Treatment groups

Experimental Treatment

Group I: Pilot Phase 1b Combination with PembrolizumabExperimental Treatment2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC

Group II: Pilot Phase 1b Combination with Cetuximab in PDACExperimental Treatment2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)

Group III: Pilot Phase 1b Combination with Cetuximab in NSCLCExperimental Treatment2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC

Group IV: Pilot Phase 1b Combination with CetuximabExperimental Treatment2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Group V: Pilot Phase 1b Combination with AfatinibExperimental Treatment2 Interventions

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC

Group VI: Phase 2 Combination with CetuximabExperimental Treatment2 Interventions

Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Group VII: Phase 2Experimental Treatment1 Intervention

Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849

Group VIII: Phase 1b ExpansionExperimental Treatment1 Intervention

Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens

Group IX: Phase 1 Dose ExplorationExperimental Treatment1 Intervention

Dose escalation of MRTX849 to determine maximum tolerated dose

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~2810

Afatinib

2016

Completed Phase 4

~2340

MRTX849

2021

Completed Phase 1

~10

Cetuximab

2011

Completed Phase 3

~2480

0 / 6Eligibility 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

Targeted cancer therapies, such as KRAS G12C inhibitors like MRTX849 (adagrasib), work by specifically targeting molecular abnormalities within cancer cells. These therapies inhibit the function of mutated proteins that drive cancer growth and survival. For instance, KRAS G12C inhibitors block the KRAS protein's activity, which is crucial for the proliferation of cancer cells with this mutation. This precision reduces damage to normal cells, leading to fewer side effects compared to traditional chemotherapy. For cancer patients, this means potentially more effective treatments with improved quality of life and better outcomes.

Novel molecular targets for the therapy of castration-resistant prostate cancer.Dynamic contrast-enhanced MRI of vascular changes induced by the VEGF-signalling inhibitor ZD4190 in human tumour xenografts.