Testing zimberelimab and domvanalimab with chemotheraphy for lung cancer

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    What is this study about?

    This clinical trial explores the effectiveness of two new medicines, zimberelimab and domvanalimab, in tandem with chemotherapy for patients with untreated metastatic non-small cell lung cancer. The study’s main goal is to compare the impact and success of this combination treatment versus a control group receiving pembrolizumab along with chemotherapy. The hopeful outcome of the trial is to identify whether the new combination of drugs can provide enhanced benefits for the involved patients. Regular health monitoring will occur during the trial to ensure patient safety.

    Learn more about this Trial

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      Locations

      Where does the clinical trial take place?

      Klagenfurt Am Woerthersee , Austria

      Linz , Austria

      Wels , Austria

      Wien , Austria

      Aalst , Belgium

      Charleroi , Belgium

      Mechelen , Belgium

      Namur , Belgium

      Boulogne-Billancourt , France

      Caen , France

      Le Mans , France

      Marseille , France

      Montpellier , France

      Nice , France

      Saint-Herblain , France

      Saint-Mandu00e9 , France

      Saint-Quentin , France

      Strasbourg , France

      Suresnes , France

      Toulon cedex , France

      Bochum , Germany

      Chemnitz , Germany

      Essen , Germany

      Freiburg , Germany

      Grosshansdorf , Germany

      Halle , Germany

      Hamburg , Germany

      Hamburg , Germany

      Hemer , Germany

      Karlsruhe , Germany

      Kassel , Germany

      Ku00f6ln , Germany

      Lubeck , Germany

      Minden , Germany

      Munchen , Germany

      Avellino , Italy

      Candiolo , Italy

      Cremona , Italy

      Genova , Italy

      Milano , Italy

      Naples , Italy

      Napoli , Italy

      Pavia , Italy

      Pesaro , Italy

      Piacenza , Italy

      Rome , Italy

      Treviglio , Italy

      Breda , Netherlands

      Ede , Netherlands

      Harderwijk , Netherlands

      Tilburg , Netherlands

      Amadora , Portugal

      Lisboa , Portugal

      Lisboa , Portugal

      Lisboa , Portugal

      Lisbon , Portugal

      Porto , Portugal

      Senhora da Hora , Portugal

      Barcelona , Spain

      Barcelona , Spain

      Barcelona , Spain

      Barcelona , Spain

      Barcelona , Spain

      Cordoba , Spain

      Girona , Spain

      Jaen , Spain

      Las Palmas de G.C. , Spain

      Madrid , Spain

      Madrid , Spain

      Madrid , Spain

      Majadahonda , Spain

      Reus , Spain

      Rincon de la Victoria , Spain

      Sevilla , Spain

      Seville , Spain

      Valencia , Spain

      Valencia , Spain

      Valencia , Spain

      London , United Kingdom


      Study Steps

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

      As a participant in this clinical trial, you will be required to take the following steps:

      1. Receive Zimberelimab (ZIM) at a dose of 360 mg and Domvanalimab (DOM) at a dose of 1200 mg, with these doses being administrated up to 35 times.
      2. Undergo chemotherapy every 3 weeks (every 21 days) on Day 1 of each cycle.
      3. The choice of chemotherapy will depend on your histology:
        1. If you have nonsquamous histology, you will receive either cisplatin at a dose of 75 mg/m2 or carboplatin AUC 5 plus pemetrexed at 500 mg/m2 every 3 weeks for the first 4 cycles. After completing the first 4 cycles, you may continue with maintenance pemetrexed at 500 mg/m2 every 3 weeks until disease progression or intolerable toxicities occur.
        2. If you have squamous histology, you will receive carboplatin AUC 6 every 3 weeks with paclitaxel at 200 mg/m2 every 3 weeks or nab-paclitaxel at 100 mg/m2 weekly for the first 4 cycles.

      These are the general steps; however, your specific treatment protocol may be adjusted based on your individual health status and the trial protocols.


      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      To join the study, you need to have pathologically documented non-small cell lung cancer (NSCLC) that meets the following criteria:

      1. Documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition).
      2. Documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations.
      3. No actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies.
      4. Have not received prior systemic treatment for metastatic NSCLC.

      Additionally, participants should not have the following diseases or conditions, which are part of the exclusion criteria:

      1. Mixed small-cell lung cancer (SCLC) and NSCLC histology.
      2. An active second malignancy or had an active second malignancy within 3 years prior to enrollment.
      3. An active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
      4. Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
      5. Active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months of enrollment.
      6. A history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

      These are disease-related criteria necessary for eligibility to participate in the clinical trial.


      Terms and conditions

      What Requirements I Have to Meet To Join This Study?

      When Am I Eligible to Join the Study?

      Below are the conditions you must meet to join the study, along with explanations of the medical terms:

      1. Life expectancy ≥ 3 months: You should be expected to live at least another three months.
      2. Pathologically documented NSCLC: You must have a diagnosis of non-small cell lung cancer (NSCLC) that is confirmed through laboratory testing, satisfying two conditions:
        1. Have documented evidence of Stage IV NSCLC disease at the time of enrollment: This means you should have the most advanced stage of NSCLC, often referred to as metastatic disease, which implies cancer has spread to other parts of the body.
        2. Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations: These genetic tests should show that you do not have mutations which are sometimes found in NSCLC, as treatments for these are different.
      3. No actionable genomic alterations: You should not have any genetic alterations in your cancer cells such as ROS1, NTRK, BRAF, RET mutations, or other changes that have specific treatments approved for them.
      4. No prior systemic treatment for metastatic NSCLC: You must not have been treated before with systemic therapy (a drug given through the bloodstream to reach cancer cells throughout the body) for cancer that has spread (metastasized).
      5. Measurable disease per RECIST v1.1 criteria by investigator assessment: Your cancer must be measurable using the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines version 1.1, which is a set of published rules that define when cancers improve (“respond”), stay the same (“stable”), or worsen (“progression”) during treatments.
      6. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1: Your level of functioning must be high, with scores meaning:
        1. Score 0: Fully active, able to carry on all pre-disease performance without restriction.
        2. Score 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
      7. Have adequate organ functions: Your organs, such as the liver, kidneys, and heart, should be functioning sufficiently well to participate in the study.

      What Reasons Could Exclude Me from the Study?

      Here is the list of key exclusion criteria for the study, with explanations of the medical terms:

      1. Mixed small-cell lung cancer (SCLC) and NSCLC histology:
      If you have a type of lung cancer that includes both small cell lung cancer (SCLC), which tends to grow and spread quickly, and non-small cell lung cancer (NSCLC), which is a category for several types of lung cancers that behave in a similar way.

      2. Positive serum pregnancy test or breastfeeding:
      You cannot participate if you are pregnant, as determined by a blood test, or if you are currently breastfeeding or planning to breastfeed during the study.

      3. Prior treatment targeting immune checkpoints:
      If you’ve previously received treatments that target immune checkpoint proteins, such as anti-PD-1 or anti-PD-L1 antibodies.

      4. Known hypersensitivity to the study drug or excipients:
      If you have a known allergy or severe reaction to the medication being studied or any of its ingredients.

      5. Active second malignancy:
      You cannot participate if you have another cancer that is currently active or if you’ve had another cancer within the past three years.

      6. Active autoimmune disease:
      You have an autoimmune disease (where the immune system attacks the body’s own cells) that has required systemic treatment in the past two years.

      7. Chronic systemic steroids:
      If you’re currently on long-term treatment with steroid medications, which can suppress the immune system.

      8. Significant third-space fluid retention:
      This refers to the accumulation of fluids in parts of the body where it doesn’t normally collect, such as in the abdominal cavity, potentially impacting organ function.

      9. Untreated CNS metastases or carcinomatous meningitis:
      If cancer has spread to your central nervous system (brain and spine) or you have carcinomatous meningitis, a condition where cancer cells are present in the meninges (the membranes that cover the brain and spinal cord).

      10. Active chronic inflammatory bowel disease:
      If you have an ongoing inflammation of the gastrointestinal tract, such as ulcerative colitis or Crohn’s disease, or if you’ve had a gastrointestinal perforation (hole in the wall of the gastrointestinal tract) within 6 months.

      11. Noninfectious pneumonitis/interstitial lung disease:
      You have a history of lung inflammation or scarring not caused by infections that required steroid treatment, or you currently have lung inflammation or scarring.

      12. Allogenic tissue/solid organ transplant:
      If you’ve had a transplant of tissue or an organ from another person.

      13. Recent live-virus vaccination:
      If you have received a live-virus vaccine within 30 days before the planned start of treatment in the study. (Note: Seasonal flu and COVID-19 vaccines without a live virus are permitted.)

      14. Active hepatitis B or C infection:
      If you currently have an infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), which affects the liver.

      Please remember that other protocol-defined criteria may apply to include or exclude participants from the study.


      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      The drugs involved in the study are:

      1. Zimberelimab (active substance: zimberelimab)
      – It is administered intravenously. This is an experimental immunotherapy drug designed to block the activity of a protein called PD-1 on the surface of T-cells, which may help the body’s immune system attack cancer cells.

      2. Domvanalimab (active substance: domvanalimab)
      – Also administered intravenously, this drug is a TIGIT inhibitor, which is another immune checkpoint targeted by immunotherapies. It is being evaluated for its potential to enhance the immune response against cancer cells.

      3. Pembrolizumab (trade name: Keytruda; active substance: pembrolizumab)
      – This is a well-known immunotherapy drug, also administered intravenously. It is a PD-1 blocking antibody used in various cancers to promote the immune system’s ability to fight cancer.

      4. Carboplatin
      – An intravenously administered chemotherapy drug used to damage the DNA of cancer cells and prevent them from dividing and growing. It is commonly used in the treatment of lung cancer.

      5. Cisplatin
      – Another intravenously administered chemotherapy drug similar to carboplatin, which works to damage cancer cell DNA.

      6. Paclitaxel
      – A chemotherapy medication given intravenously, paclitaxel works by inhibiting cell division, which is critical in cancer treatment.

      7. Nab-paclitaxel
      – A formulation of paclitaxel attached to albumin nanoparticles to improve drug delivery to the tumor. It is administered intravenously.

      8. Pemetrexed
      – Administered intravenously, it is a chemotherapy drug that disrupts folate-dependent metabolic processes essential for cell replication.

      In the context of this study, these drugs are combined in different arms to assess their comparative effectiveness in treating patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration. The study compares the effects of zimberelimab and domvanalimab in combination with chemotherapy relative to pembrolizumab combined with chemotherapy on progression-free survival (PFS) and overall survival (OS).

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

      The active substances participating in the clinical trial are known to medicine and are present in medical literature. Here is the list of substances along with a description of each:

      1. Paclitaxel: Known as a plant alkaloid derived from the bark of the Pacific yew tree, Paclitaxel is widely used as an antineoplastic agent in various cancer treatments. It is classified under the category of antineoplastic agents, phytogenic, tubulin modulators, and antimitotic agents, indicating its role in disrupting cell division.
      2. Albumin-Bound Paclitaxel: This formulation of Paclitaxel is designed to improve the solubility and delivery of Paclitaxel to tumor cells. The albumin-bound form is also an antineoplastic, specifically under the tubulin modulators, which interfere with microtubules in cells.
      3. Carboplatin: Carboplatin is a chemotherapy drug used to treat various types of cancer. It belongs to a group of cancer-fighting medications known as alkylating agents and is considered less toxic compared to similar drugs.
      4. Pembrolizumab: This is an immunotherapy drug that works as an immune checkpoint inhibitor to help the immune system recognize and fight cancer cells. It is frequently used in the treatment of advanced cancers, including lung cancer.
      5. Pemetrexed: Pemetrexed is a chemotherapeutic agent that belongs to the class of folic acid antagonists. It acts as an antifolate inhibiting the formation of purine and pyrimidine, which are necessary for the synthesis and repair of DNA, thereby arresting the growth of rapidly dividing tumor cells.

      These substances are confirmed to be part of conventional anti-cancer pharmacotherapy and have established mechanisms of action as recognized in medical practice and research.


      Study ID

      CT-EU-00019898

      Recruitment status

      Recruting new patients

      Start of the trial

      2 years ago