Study of savolitinib and osimertinib Vs chemotherapy in advancing lung cancer

Recruting new patients

Select region:

Navigation:

    What is this study about?

    This clinical trial will include approximately 324 people with a specific type of advanced lung cancer that has not improved with a specific treatment, osimertinib. People in this study will receive a combination of two drugs, savolitinib and osimertinib, or standard chemotherapy. The aim is to find out which treatment is more effective and safe. A person’s cancer will be monitored to see how it responds to treatment. If the cancer gets worse or the side effects become too much to bear, the person may stop participating in the study. The study will measure responses such as the number of people who see improvement in their cancer treatment, the time it takes for symptoms to get worse and the presence of drugs in the body.

    Learn more about this Trial

      I accept the Terms of Use and Privacy Policy*

       I consent to the Service Operator sending commercial information*

      I consent to the Service Operator using telecommunications terminal devices and automatic calling systems in marketing communications*

      Success

      Your form submitted successfully!

      Error

      Sorry! your form was not submitted properly, Please check the errors above.

      Locations

      Where does the clinical trial take place?

      Salzburg , Austria

      Bruxelles , Belgium

      Edegem , Belgium

      Gent , Belgium

      Hasselt , Belgium

      Mons , Belgium

      Roeselare , Belgium

      Sint-Niklaas , Belgium

      Haskovo , Bulgaria

      Pleven , Bulgaria

      Plovdiv , Bulgaria

      Vratsa , Bulgaria

      Angers , France

      Bobigny , France

      Bordeaux Cedex , France

      Brest , France

      Creteil , France

      Dijon , France

      Marseille , France

      Paris , France

      Paris , France

      Poitiers , France

      Rennes Cedex 9 , France

      Rouen , France

      Saint-Herblain , France

      Saint-Quentin cedex , France

      Strasbourg Cedex , France

      Suresnes Cedex , France

      Berlin , Germany

      Berlin , Germany

      Chemnitz , Germany

      Frankfurt A. Main , Germany

      Gauting , Germany

      Immenhausen , Germany

      Lu00f6wenstein , Germany

      Muenster , Germany

      Mu00fcnchen , Germany

      Wangen , Germany

      Athens , Greece

      Athens , Greece

      Chaidari , Greece

      Heraklion , Greece

      Larissa , Greece

      Rio , Greece

      Thessaloniki , Greece

      Thessaloniki , Greece

      Avellino , Italy

      Aviano , Italy

      Catania , Italy

      Meldola , Italy

      Milano , Italy

      Milan , Italy

      Modena , Italy

      Monserrato , Italy

      Napoli , Italy

      Orbassano , Italy

      Padova , Italy

      Parma , Italy

      Perugia , Italy

      Peschiera Del Garda , Italy

      Roma , Italy

      Roma , Italy

      Treviso , Italy

      Bialystok , Poland

      Krakow , Poland

      Olsztyn , Poland

      u0141u00f3du017a , Poland

      Badajoz , Spain

      Badalona , Spain

      Barcelona , Spain

      Barcelona , Spain

      Cordoba , Spain

      Girona , Spain

      La Coruu00f1a , Spain

      Madrid , Spain

      Madrid , Spain

      Majadahonda , Spain

      Mu00e1laga , Spain

      Pontevedra , Spain

      Sabadell , Spain

      Sevilla , Spain

      Valencia , Spain

      Zaragoza , Spain

      Bristol , United Kingdom

      London , United Kingdom

      Manchester , United Kingdom

      Wolverhampton , United Kingdom


      Study Steps

      How Complex Will My Study Be and What Phases Will I Go Through?

      In this clinical trial, patients have two main options depending on the group they are randomized into:

      1. Chemotherapy Arm
        • Patients will receive Pemetrexed (500 mg/m^2) with either Cisplatin (75 mg/m^2) or Carboplatin (AUC5) on Day 1 of 21-day cycles for 4 cycles, followed by Pemetrexed maintenance (500 mg/m^2) every 3 weeks (Q3W).
      2. Savolitinib + Osimertinib Arm
        • Patients will take 300 mg of Savolitinib (administered as three 100 mg tablets twice daily) along with 80 mg of Osimertinib (administered as one 80 mg tablet once daily). Both medications are taken orally.

      Patients will continue treatment until they meet any of the following criteria: objective progression of disease (based on RECIST 1.1) as assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.


      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      To be eligible to join the study based on the disease requirements, you need to have:

      1. Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to curative therapy.
      2. At least one documented sensitizing EGFR mutation, which can include an exon 19 deletion, L858R mutation, and/or T790M.
      3. Documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy.
      4. MET overexpression and/or amplification in a tumor specimen collected following progression on prior osimertinib treatment.
      5. Measurable disease as defined by RECIST 1.1 criteria.

      These are the disease-specific conditions you need to meet to potentially participate in the study.


      Terms and conditions

      What Requirements I Have to Meet To Join This Study?

      When Am I Eligible to Join the Study?

      The inclusion criteria for joining the study are as follows:

      1. Signed and dated Informed Consent Form (ICF): Provision of a signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling, and analyses.
      2. Age Requirement: You must be 18 years or older (or 20 years or older in Japan) at the time of signing the informed consent.
      3. Diagnosis: Histologically or cytologically confirmed locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) that is not amenable to curative therapy.
      4. EGFR Mutation: You must have at least one documented sensitizing EGFR mutation, which includes exon 19 deletion, L858R mutation, and/or T790M mutation.
      5. Disease Progression: There needs to be documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy.
      6. Tissue Provision: Mandatory provision of formalin-fixed paraffin-embedded (FFPE) tumor tissue is required.
      7. Met Overexpression/Amplification: MET overexpression and/or amplification must be present in the tumor specimen collected following progression on prior osimertinib treatment.
      8. Measurable Disease: You should have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). RECIST 1.1 is a set of published rules that define when cancer patients improve (“respond”), stay the same (“stable”), or worsen (“progression”) during treatments.
      9. Adequate Organ Functions: You must have adequate hematological, liver, renal (kidney), cardiac (heart) functions, and coagulation parameters.
      10. ECOG Performance Status: An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 is required, with 0 indicating you are fully active and able to carry on all pre-disease activities without restriction, and 1 indicating you are restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.

      What Reasons Could Exclude Me from the Study?

      Here is a list of conditions that would exclude you from taking part in the study, along with explanations of medical terms where applicable:

      1. Predominant squamous NSCLC, and small cell lung cancer: If the primary type of non-small cell lung cancer (NSCLC) is squamous or if you have small cell lung cancer, you are excluded.
      2. Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib: Previous or ongoing treatment with third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), except for Osimertinib, would exclude you.
      3. Prior or current treatment with savolitinib or another MET inhibitors: Previous or current treatment with savolitinib or other MET (mesenchymal-epithelial transition factor) inhibitors would exclude you.
      4. Spinal cord compression or brain metastases: These conditions could exclude you unless they are asymptomatic and stable.
      5. History or active leptomeningeal carcinomatosis: This condition refers to cancer spread to the layers of tissue covering the brain and spinal cord.
      6. Unresolved toxicities from any prior therapy greater than CTCAE Grade 1: If you have unresolved side effects from previous treatments that are more severe than Grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE), except for certain exceptions, you are excluded.
      7. Active/unstable cardiac diseases: Any current or recent (within the last 6 months) heart diseases, significant electrocardiogram (ECG) abnormalities, or anything that may affect QTc intervals could exclude you.
      8. History of liver cirrhosis of any origin: A medical history of liver cirrhosis, a condition characterized by scarring of the liver or other significant liver diseases, would exclude you.
      9. Known serious active infection: Having an active serious infection, such as tuberculosis or HIV, hepatitis B or C virus (HBV or HCV), or a significant gastrointestinal disease, could exclude you.
      10. Receipt of live attenuated vaccine: If you received a live attenuated vaccine, including COVID-19 vaccines, within 30 days before the first dose of the study drug, you are excluded.
      11. Past medical history of ILD, drug-induced ILD, radiation pneumonitis: A history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any signs of currently active ILD, would exclude you.
      12. Medications affecting cytochrome P450 enzymes: If you are taking medications or herbal supplements that are strong inducers of CYP3A4 or strong inhibitors of CYP1A2, enzymes important in drug metabolism, you may be excluded from the study.

      Please let me know if you need further clarification on any of these points.


      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      The clinical study involves the following drugs, and I have included a brief description of each active substance:

      1. Savolitinib (AZD6094, HMPL-504, volitinib): Savolitinib is an oral medication used as a selective inhibitor of the c-Met receptor tyrosine kinase. It is being studied for its potential in treating various types of cancer, including those where the MET gene is altered, leading to c-Met dysregulation and proliferation of cancer cells.
      2. Osimertinib (AZD9291, Tagrisso): Osimertinib is an oral medication that is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). It is specifically designed to inhibit both EGFR-sensitizing mutations and EGFR T790M resistance mutations. It is primarily used for the treatment of certain types of non-small cell lung cancer.
      3. Pemetrexed: Pemetrexed is administered through an IV infusion and is known as a multitargeted antifolate. It disrupts folate-dependent metabolic processes that are essential for cell replication. It’s often used for the treatment of pleural mesothelioma and non-squamous non-small cell lung cancer.
      4. Cisplatin: Cisplatin is administered through an IV infusion and is a platinum-based drug that is used as a chemotherapy agent. It forms cross-links with DNA and causes apoptosis, which is particularly effective in the treatment of various types of cancers, including testicular, ovarian, and bladder cancers, as well as non-small cell lung cancer.
      5. Carboplatin: Carboplatin, also administered through an IV infusion, is another form of platinum-based chemotherapy. Similar to cisplatin, it interferes with DNA repair mechanisms leading to apoptosis. This drug is used to treat various solid tumor cancers including ovarian, lung, and head and neck cancers.

      Have the Medicinal Substances Used in the Trial Been Previously Studied in Medicine?

      The active substances involved in the clinical trial and their known status in medicine and medical literature are:

      1. Savolitinib: Known in the medical literature and its pharmacokinetics are being investigated in this trial. Plasma concentrations of savolitinib and its metabolites will be studied.
      2. Osimertinib: This is a drug that is known in medicine and has been used in various treatments before. It is part of this clinical trial where it is administered orally in combination with savolitinib.
      3. Pemetrexed: A known chemotherapeutic agent used in the treatment of various types of cancer. In the context of this trial, it is used as a comparator and is administered via IV infusion.
      4. Cisplatin: An extensively studied and well-known chemotherapeutic drug. It is being used alongside pemetrexed as part of the platinum-based doublet chemotherapy comparator arm in the trial and is administered via IV infusion.
      5. Carboplatin: Similar to cisplatin, carboplatin is a known platinum-based chemotherapy drug. It is used in the trial as part of the comparator arm for the study and is administered via IV infusion.

      Each of these substances has been known to the medical community and has been described in the medical literature prior to this trial. The study aims to investigate the efficacy and safety of the combination of savolitinib and osimertinib specifically in the context of advanced or metastatic NSCLC that has progressed following osimertinib treatment.


      Study ID

      CT-EU-00029524

      Recruitment status

      Recruting new patients

      Start of the trial

      2 years ago

      Study phase

      Phase
      III