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Clinical Trials for KRAS Gene Mutation

Currently, 8 clinical trials are being conducted across Europe to evaluate new treatments for cancers with KRAS gene mutations, specifically the KRAS G12C mutation. These trials are testing various targeted therapies either alone or in combination with other medications for conditions including non-small cell lung cancer and colorectal cancer. Trials are available in multiple European countries, offering patients access to innovative treatment options.

Clinical trial locations

Study of MK-1084, cetuximab and mFOLFOX6 combination compared to mFOLFOX6 with or without bevacizumab for patients with KRAS G12C-mutant advanced colorectal cancer

This trial focuses on patients with advanced colorectal cancer that has the KRAS G12C mutation and cannot be surgically removed or has spread to other parts of the body. The study tests a new drug called MK-1084 in combination with cetuximab (a targeted therapy) and mFOLFOX6 (a chemotherapy regimen containing oxaliplatin, fluorouracil, and calcium folinate).

Inclusion criteria: Participants must have confirmed advanced colorectal cancer at Stage III or IV with documented KRAS G12C mutation in tumor tissue. Those enrolled in Part 2 of the study must not have received any previous treatments for advanced or metastatic disease. Patients must be at least 18 years old. Those with well-controlled HIV, Hepatitis B (on antiviral treatment with undetectable virus levels), or a history of Hepatitis C (with undetectable virus) may participate.

Exclusion criteria: The trial excludes patients with active brain metastases or brain/spinal cord conditions, those previously treated with any KRAS G12C inhibitor, and individuals with known allergies to study medications. Patients with active autoimmune disease requiring systemic treatment, uncontrolled high blood pressure, major surgery within 4 weeks before starting treatment, or participation in another clinical trial are not eligible. Those with serious heart conditions (including heart attack within the past 6 months, unstable chest pain, or severe heart rhythm problems), active or chronic hepatitis infections, or history of other cancers within the past 3 years (except successfully treated non-melanoma skin cancer or early-stage cancer that has been completely removed) cannot participate. Pregnant or breastfeeding women are also excluded.

Main focus: The trial aims to determine whether adding MK-1084 and cetuximab to standard chemotherapy is safe and effective for treating this specific type of colorectal cancer. One group will receive MK-1084, cetuximab, and mFOLFOX6, while the comparison group will receive mFOLFOX6 with or without bevacizumab (a drug that blocks blood vessel formation to tumors).

Investigational drugs: MK-1084 is an investigational targeted therapy taken as oral tablets, specifically designed for KRAS G12C-mutant colorectal cancer. Cetuximab is an approved antibody therapy administered intravenously that targets EGFR protein on cancer cells. mFOLFOX6 is a standard chemotherapy combination, and bevacizumab is an established medication that works by cutting off blood supply to tumors.

Study on Sotorasib for Patients with Advanced KRAS G12C-Mutated Non-Small Cell Lung Cancer and Comorbidities

This trial evaluates sotorasib, a medication taken as film-coated tablets, for patients with non-small cell lung cancer that has the KRAS G12C mutation. The study particularly focuses on patients who may have additional health conditions.

Inclusion criteria: Participants must have confirmed advanced non-small cell lung cancer at Stage III or IV with documented KRAS G12C mutation. For Part 2 of the study, patients must have received platinum-based chemotherapy and immune checkpoint inhibitor therapy unless they were not eligible for these treatments. Participants must have an ECOG performance status of 0-1 (meaning they are fully active or have some restrictions but can still carry out light work), a life expectancy of at least 12 weeks, and at least one measurable tumor that has not been treated with radiation. Patients must be at least 18 years old, have adequate bone marrow and organ function, and meet specific heart rhythm criteria (QTc less than 470 milliseconds for females or less than 450 milliseconds for males).

Exclusion criteria: The trial excludes patients without the KRAS G12C mutation, those outside the specified age range, and vulnerable populations that cannot be safely included in the study.

Main focus: The study aims to evaluate how effective sotorasib is in reducing tumor size in patients with this specific type of lung cancer. Researchers will measure the Objective Response Rate (the percentage of patients whose tumors shrink or disappear), progression-free survival (time during and after treatment that the cancer does not worsen), duration of response, and overall survival.

Investigational drug: Sotorasib is an enzyme inhibitor that works by blocking the KRAS G12C mutated protein, which helps cancer cells grow. By targeting this specific mutation, the medication aims to slow down or stop cancer progression.

Study of JDQ443 and Ribociclib in Combination for Adult Patients with Advanced Solid Tumors with KRAS G12C Mutation

This trial studies various treatment combinations for patients with advanced cancers that have the KRAS G12C mutation. The types of cancer being studied include non-small cell lung cancer, colorectal cancer, pancreatic duct adenocarcinoma, and biliary tract cancer.

Inclusion criteria: Participants must have advanced cancer with confirmed KRAS G12C mutation that has spread to other parts of the body and cannot be removed by surgery. In the dose escalation phase, patients should have already received standard treatment or be unable to receive it. For Phase II, patients with non-small cell lung cancer must have received platinum-based chemotherapy and immune checkpoint inhibitor therapy unless not eligible. Those with colorectal cancer must have received specific chemotherapy treatments unless not eligible. All participants must have an ECOG performance status of 0 or 1, have a part of their disease that can be biopsied, and be at least 18 years old.

Exclusion criteria: The trial excludes patients without the KRAS G12C mutation, those whose cancer is not advanced, non-adults, patients unable to understand or agree to study requirements, and vulnerable populations needing special protection.

Main focus: The study is divided into two phases. The first phase involves gradually increasing the dose of medications to determine the safest and most effective dose. The second phase assesses how well the treatments work in controlling the cancer. The study explores JDQ443 alone and in combination with LEE011 (ribociclib), Mekinist (trametinib), and cetuximab.

Investigational drug: JDQ443 is an experimental medication taken as tablets, designed to target the KRAS G12C mutation. The trial is exploring its safety, tolerability, and effectiveness in potentially slowing down or stopping tumor growth when used alone or with other cancer treatments.

Study Comparing Divarasib, Sotorasib, and Adagrasib for Patients with Advanced or Metastatic KRAS G12C-Positive Non-Small Cell Lung Cancer

This trial compares three different medications for treating non-small cell lung cancer with the KRAS G12C mutation: a new treatment called divarasib and two existing treatments, sotorasib and adagrasib. All are taken as film-coated tablets.

Inclusion criteria: Participants must have advanced or metastatic non-small cell lung cancer with confirmed KRAS G12C mutation verified by a reliable lab test. The cancer must be measurable according to RECIST v1.1 guidelines. Patients must also have testing for KEAP1 mutation, provide a tumor tissue sample with a pathologist’s report, and have negative tests for HIV, hepatitis B, and hepatitis C. Adequate blood and organ function is required, as verified by tests within 14 days before starting treatment. Both male and female patients are eligible.

Exclusion criteria: The trial excludes patients with different types of cancer than specified, those not within the specified age range, patients unable to follow study procedures or take medications as required, those with serious health conditions that might interfere with the study, pregnant or breastfeeding women, and patients with recent participation in other clinical trials. Those with allergies to study medications, inability to provide informed consent, or inability to swallow oral medications are also excluded.

Main focus: The study evaluates how well these treatments work in preventing the cancer from getting worse (progression-free survival). Participants will be randomly assigned to receive either divarasib, sotorasib (LUMYKRAS 120 mg), adagrasib (KRAZATI 200 mg), or a placebo. Regular check-ups and tests will assess health and cancer status throughout the study.

Investigational drugs: Divarasib is a medication being evaluated for its effectiveness compared to the other treatments. Sotorasib and adagrasib are treatments that work by targeting and inhibiting the KRAS G12C mutated protein to help stop cancer growth and spread.

Study of adagrasib in elderly patients (70 years or older) or patients with poor performance status who have KRAS G12C mutation-positive non-small cell lung cancer

This study focuses specifically on treating elderly individuals (70 years and older) and those who have more difficulty performing daily activities due to their stage IV non-small cell lung cancer with the KRAS G12C mutation.

Inclusion criteria: Participants must be at least 18 years old with confirmed stage IV non-small cell lung cancer and a verified KRAS G12C mutation confirmed by tissue or blood testing. They must have received at least one previous treatment for lung cancer (such as chemotherapy or immunotherapy), have a life expectancy of at least 12 weeks, and have measurable disease that can be monitored through scans. Participants must belong to one of two groups: Group 1 (age 18 or older with limited ability to perform daily activities, ECOG PS=2) or Group 2 (age 70 or older with good ability to perform daily activities, ECOG PS=0-1). They must have adequate blood cell counts and proper kidney and liver function, provide written informed consent, and if able to become pregnant, have a negative pregnancy test.

Exclusion criteria: The trial excludes patients with prior treatment with a KRAS G12C inhibitor, active or untreated brain metastases, history of other cancers within the past 3 years (except successfully treated non-melanoma skin cancer or cervical cancer in situ), and significant heart conditions (including heart attack within the past 6 months, unstable angina, or heart failure requiring treatment). Those with active uncontrolled infections, known allergy to study medication, pregnancy or breastfeeding, inability to swallow oral medications, serious medical conditions that could interfere with participation, current participation in other clinical trials or use of investigational drugs within 28 days, and any condition that would make participation unsafe are also excluded.

Main focus: The trial evaluates how well adagrasib works in treating two specific groups of patients who may be more vulnerable due to age or reduced physical functioning. Treatment may continue for up to 13 months, with regular check-ups to monitor effectiveness and side effects. The maximum daily dose is 1200 milligrams.

Investigational drug: Adagrasib is a targeted therapy medication taken orally that specifically blocks the abnormal KRAS G12C protein that helps cancer cells grow and spread. It is designed to help patients who may be elderly or have limited physical functioning due to their condition.

Study of BMS-986466 with Adagrasib and Cetuximab for Patients with KRAS G12C-mutant Advanced Solid Tumors

This trial tests a new treatment combination involving BMS-986466 with adagrasib, and in some cases cetuximab, for patients with advanced solid tumors that have the KRAS G12C mutation. The types of cancer being studied include non-small cell lung cancer, colorectal cancer, pancreatic duct adenocarcinoma, and biliary tract cancer.

Inclusion criteria: Participants must have confirmed diagnosis of advanced cancer with a KRAS G12C mutation, including non-small cell lung cancer, colorectal cancer, pancreatic duct adenocarcinoma, and biliary tract cancer. The cancer must have spread to other parts of the body and cannot be removed by surgery. Patients may or may not have received previous treatment with KRAS G12C inhibitors. For non-small cell lung cancer and colorectal cancer, participants must have documented KRAS G12C mutation from an approved test, or if unavailable, confirmed by a central laboratory during screening. Participants must have tried standard treatments that either did not respond, could not be tolerated, or the cancer returned after treatment. For Part 2 of the study, participants must not have been treated with KRAS G12C inhibitors before. Participants must be at least 18 years old.

Exclusion criteria: The trial excludes patients with other types of cancer without the specific KRAS G12C mutation, those previously treated with a KRAS G12C inhibitor, patients not within the specified age range, those unable to follow study procedures, patients with certain medical conditions that might interfere with treatment evaluation, pregnant or breastfeeding women, those participating in another clinical trial simultaneously, patients with history of severe allergic reactions to study medications, and those with uncontrolled medical conditions that could make participation unsafe.

Main focus: The study is divided into two parts. Part 1 aims to find the safest dose that patients can tolerate. Part 2 compares the effectiveness of treatment combinations. For patients with non-small cell lung cancer, the study compares BMS-986466 with adagrasib against adagrasib alone. For those with colorectal cancer, it compares BMS-986466 with adagrasib and possibly cetuximab against adagrasib plus cetuximab.

Investigational drugs: BMS-986466 is an experimental drug being tested to determine if it can work together with other cancer treatments to stop or slow tumor growth. Adagrasib is a medication that targets the KRAS G12C mutation by blocking signals that tell cancer cells to grow and divide. Cetuximab is a monoclonal antibody used to treat certain types of cancer by targeting a protein on the surface of cancer cells, potentially slowing down or stopping tumor growth.

Study of JDQ443, TNO155, and Tislelizumab for Patients with Advanced Solid Tumors with KRAS G12C Mutation

This trial tests a new treatment called JDQ443, both on its own and in combination with TNO155 and tislelizumab, for patients with advanced solid tumors that have the KRAS G12C mutation.

Inclusion criteria: Patients must have advanced solid tumors with the KRAS G12C mutation. For the dose escalation part, patients should have advanced tumors that cannot be removed by surgery or have spread to other parts of the body, and they should have tried standard treatments or cannot tolerate them. For the dose expansion part, patients with advanced non-small cell lung cancer must have received platinum-based chemotherapy and immune checkpoint inhibitor therapy unless they were not eligible, and must not have been treated with a KRAS G12C inhibitor before. Patients with advanced colorectal cancer must have received standard treatments including specific chemotherapy types unless not eligible, and must not have been treated with a KRAS G12C inhibitor before. Patients with advanced solid tumors other than non-small cell lung cancer or colorectal cancer must have tried standard treatments or cannot tolerate them, and must not have been treated with a KRAS G12C inhibitor before. All patients must have a performance status of 0 or 1, have a tumor that can be biopsied, and be at least 18 years old.

Exclusion criteria: The trial excludes patients without advanced solid tumors with the KRAS G12C mutation, those not within the specified age range, patients unable to safely tolerate study medications, those unable to follow study procedures or attend all required visits, and vulnerable populations that the study cannot safely include.

Main focus: The study is conducted in two main parts. The first part focuses on finding the best dose of JDQ443 alone and in combination with other treatments. The second part evaluates how effective these treatments are in shrinking tumors and improving patient condition. Throughout the study, the safety of the treatments will be closely monitored.

Investigational drugs: JDQ443 is a medication being studied for its potential to treat advanced solid tumors with the KRAS G12C mutation, taken as tablets. TNO155 is being combined with JDQ443 to see if the combination can improve treatment outcomes, taken as capsules. Tislelizumab is an additional medication being tested in combination with JDQ443, and also with JDQ443 and TNO155 together, given as an infusion, to assess whether it can enhance anti-tumor effects.

Study of Sotorasib Treatment in Patients with Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation Who Have Previously Received Treatment

This French study focuses on non-small cell lung cancer that has spread to other parts of the body or is locally advanced and cannot be surgically removed, specifically in cases with the KRAS G12C mutation. The study involves patients who have already received at least one previous treatment.

Inclusion criteria: Participants must be at least 18 years old, have health insurance coverage through a Social Security System, and have good physical performance status (ECOG score of 0 or 1, meaning able to carry out light daily activities). They must have advanced lung cancer that cannot be surgically removed or has spread to other parts of the body with the KRAS G12C mutation, have received at least one previous treatment for advanced cancer and experienced disease progression or recurrence, and have a life expectancy of more than 3 months. Participants must have tumors that can be easily biopsied and agree to undergo biopsies before, during, and after treatment. They must have adequate bone marrow and organ function based on laboratory tests performed within 14 days before joining the study, and be able to read, understand, and sign the informed consent form before any study procedures begin.

Exclusion criteria: The trial excludes patients with history of treatment with a KRAS G12C inhibitor, active brain metastases that are not treated and stable, known severe allergic reaction to sotorasib or its components, pregnant or breastfeeding women, and significant heart conditions (including uncontrolled high blood pressure, unstable heart disease, or heart attack within the last 6 months). Those with active infections requiring systemic treatment, other active cancers requiring treatment (except certain skin cancers or in situ cervical cancer), severe liver dysfunction, severe kidney disease requiring dialysis, any medical condition that could interfere with safe administration of study treatment, inability to swallow oral medications, and participation in another clinical trial within 30 days before starting this study are also excluded.

Main focus: The study aims to understand how tumors respond to treatment after 4 months and to identify biological markers that might explain why some patients stop responding to treatment. Participants will take sotorasib tablets daily and have regular medical check-ups and imaging scans every 8 weeks. The study also includes collecting tissue samples before, during, and after treatment.

Investigational drug: Sotorasib (LUMYKRAS or AMG 510) is a targeted therapy medication taken orally that works by blocking the abnormal KRAS protein that helps cancer cells grow and spread. It is used in patients who have already received previous treatment for their locally advanced or metastatic lung cancer and is designed to specifically target cancer cells with the KRAS G12C mutation.

Summary

The 8 clinical trials for KRAS G12C mutation focus predominantly on two main cancer types: non-small cell lung cancer and colorectal cancer. A notable observation is the concentration of trials in France, which participates in 7 out of 8 studies, making it the country with the broadest availability of these trials. Spain, Italy, and Belgium also have strong representation, participating in 6, 6, and 5 trials respectively.

Several investigational drugs appear across multiple trials, indicating their importance in KRAS G12C-targeted therapy research. Sotorasib is being studied in 3 separate trials, while adagrasib appears in 4 different studies. The newer investigational drug JDQ443 is being evaluated in 2 trials in various combination approaches. Many trials explore combination therapies rather than single-agent treatments, reflecting the evolving understanding that combining targeted therapies may provide better outcomes for patients with this specific genetic mutation.

An important aspect of these trials is their focus on specific patient populations, including elderly patients (70 years or older) and those with reduced physical functioning. This demonstrates a commitment to developing treatment options for patients who might otherwise have limited therapeutic choices. The trials typically require confirmation of the KRAS G12C mutation through reliable laboratory testing, emphasizing the importance of precision medicine in modern cancer treatment.

Ongoing Clinical Trials on K-ras gene mutation

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