Study of Dato-DXd and durvalumab in persistent triple-negative breast cancer

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    What is this study about?

    This trial is about testing a combination of new treatments for triple-negative breast cancer which hasn’t fully responded to the first line of treatment. The new treatment includes a drug called Dato-DXd and a known drug called Durvalumab, both administered individually, or as a combination. This is compared to an already established treatment recommended by the doctor. The researchers are mainly interested in delaying the return of the cancer, and if the new drug with or without Durvalumab does a better job at this than the doctor-recommended treatment. Along with this main goal, the trial will also monitor how these treatments affect patients’ routine activities, their well-being, their levels of fatigue, the amount of Dato-DXd and related components present in the body, and any side effects and potential risks associated with these treatments.

    Learn more about this Trial

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      Locations

      Where does the clinical trial take place?

      Anderlecht , Belgium

      Brussel , Belgium

      Bruxelles , Belgium

      Charleroi , Belgium

      Edegem , Belgium

      Gent , Belgium

      Hasselt , Belgium

      Liu00e8ge , Belgium

      Namur , Belgium

      Sint-Niklaas , Belgium

      Wilrijk , Belgium

      Aalborg , Denmark

      Copenhagen , Denmark

      Herlev , Denmark

      Herning , Denmark

      Nu00e6stved , Denmark

      Odense C , Denmark

      Su00f8nderborg , Denmark

      Vejle , Denmark

      Angers Cedex 02 , France

      Bordeaux , France

      Dijon , France

      Epagny Metz-Tessy , France

      Lyon , France

      Montpellier , France

      Nimes , France

      Paris Cedex 05 , France

      Poitiers , France

      Saint Herblain Cedex , France

      Vandoeuvre Les Nancy , France

      Villejuif Cedex , France

      Augsburg , Germany

      Berlin , Germany

      Frankfurt am Main , Germany

      Hamburg , Germany

      Hannover , Germany

      Heilbronn , Germany

      Kiel , Germany

      Langen , Germany

      Leipzig , Germany

      Ludwigsburg , Germany

      Mu00f6nchengladbach , Germany

      Mu00fcnchen , Germany

      Paderborn , Germany

      Regensburg , Germany

      Stuttgart , Germany

      Troisdorf , Germany

      Tu00fcbingen , Germany

      Witten , Germany

      Wuppertal , Germany

      Athens , Greece

      Athens , Greece

      Athens , Greece

      Athens , Greece

      Athens , Greece

      Heraklion , Greece

      Patras , Greece

      Thessaloniki , Greece

      Thessaloniki , Greece

      Bologna , Italy

      Brescia , Italy

      Firenze , Italy

      Genova , Italy

      Livorno , Italy

      Meldola , Italy

      Messina , Italy

      Milano , Italy

      Milan , Italy

      Napoli , Italy

      Padova , Italy

      Roma , Italy

      Rozzano , Italy

      Barcelona , Spain

      Barcelona , Spain

      Bilbao (Vizcaya) , Spain

      Elche(Alicante) , Spain

      Madrid , Spain

      Madrid , Spain

      Malaga , Spain

      Palma de Mallorca , Spain

      Toledo , Spain

      Valencia , Spain

      Gu00f6teborg , Sweden

      Ju00f6nku00f6ping , Sweden

      Malmu00f6 , Sweden

      Stockholm , Sweden

      Stockholm , Sweden

      Stockholm , Sweden

      Sundsvall , Sweden

      Uppsala , Sweden

      Cambridge , United Kingdom

      Cardiff , United Kingdom

      Derry , United Kingdom

      Edinburgh , United Kingdom

      Greater London , United Kingdom

      London , United Kingdom

      London , United Kingdom

      Manchester , United Kingdom

      Newcastle upon Tyne , United Kingdom

      Portsmouth , United Kingdom

      Surrey , United Kingdom

      Taunton , United Kingdom


      Study Steps

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

      The steps a patient needs to take in this clinical trial depend on the arm they are allocated to. For example, in one of the arms labeled “Dato-DXd in combination with Durvalumab”:

      1. The patient will receive Dato-DXd at a dose of 6 mg/kg intravenously (IV) every 3 weeks (Q3W) for a total of 8 cycles.
      2. In combination with Dato-DXd, the patient will also receive Durvalumab at a dose of 1120 mg IV Q3W for a total of 9 cycles.

      Please let me know if you need detailed information for the other arms within this clinical trial.


      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      To join the clinical trial, you need to have the following disease:

      Histologically confirmed invasive Triple Negative Breast Cancer (TNBC), as defined by the ASCO/CAP guidelines. Moreover, there must be residual invasive disease in the breast and/or axillary lymph node(s) at surgical resection following neoadjuvant therapy, and no evidence of locoregional or distant relapse.

      Exclusion criteria related to diseases or conditions include:

      1. Stage IV (metastatic) TNBC.
      2. History of prior invasive breast cancer, or evidence of recurrent disease following preoperative therapy and surgery.
      3. Severe or uncontrolled medical conditions, including systemic diseases, history of allogeneic organ transplant and active bleeding diseases, ongoing or active infection, serious chronic gastrointestinal conditions associated with diarrhea, chronic diverticulitis or previous complicated diverticulitis.
      4. History of another primary malignancy except for adequately resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, in situ disease (including ductal carcinoma in situ) that has undergone potentially curative therapy, or other solid malignancy treated with curative intent with no known active disease within 5 years before randomisation and of low potential risk for recurrence.

      Please ensure you meet these disease-related criteria to be eligible to 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?

      Inclusion Criteria:

      1. Age: Participants must be ≥ 18 years at the time of screening.
      2. Histologically Confirmed Invasive TNBC: TNBC stands for Triple-Negative Breast Cancer, which is a type of breast cancer that does not have receptors for estrogen, progesterone, or HER2/neu, making it more challenging to treat. Confirmation is done via tissue analysis according to the ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.
      3. Residual Invasive Disease: After completing neoadjuvant therapy, participants must have residual invasive disease in the breast and/or axillary lymph node(s) evident during surgical resection.
      4. Neoadjuvant Therapy Completion: Participants must have completed at least 6 cycles of neoadjuvant therapy featuring an anthracycline and/or a taxane, with or without platinum chemotherapy, and with or without pembrolizumab.
      5. No Evidence of Relapse: Participants should show no signs of locoregional (local) or distant (spread to other body parts) cancer relapse.
      6. Surgical Removal: All clinically evident disease in the breast and lymph nodes must have been surgically removed.
      7. ECOG Performance Status: ECOG stands for Eastern Cooperative Oncology Group, which is a scale used to determine the activity level and the ability to care for oneself. Participants must have a performance status of 0 (fully active, able to carry on all pre-disease performance without restriction) or 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).
      8. Tumor Sample: All participants must provide a Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample from the surgery of the residual invasive disease for tissue-based analysis.
      9. No Adjuvant Systemic Therapy: Participants must not be undergoing any adjuvant systemic therapy before the study.
      10. Radiotherapy Completion: If radiotherapy is applicable, it must be completed prior to the initiation of the study intervention.
      11. Randomization Timing: There are specific intervals mentioned between completion of radiotherapy or surgery and the date of randomization into the study, depending on whether the participant has undergone post-operative radiation therapy.
      12. LVEF ≥ 50%: Participants must have a Left Ventricular Ejection Fraction of at least 50%, which measures how much blood the left ventricle of the heart pumps out with each contraction. Assessment should be via Echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan within 28 days before randomisation.
      13. Eligible for Therapy Options: Participants should be eligible for one of the therapy options listed as per the investigator’s assessment.
      14. No Known Germline BRCA Mutations: Participants should not have any known pathogenic mutations in BRCA1 or BRCA2 genes, which are associated with increased risk of breast and ovarian cancers.
      15. Adequate Bone Marrow Reserve and Organ Function: This criterion ensures that the participant’s body can tolerate the treatment. The assessment should be within 7 days before randomisation.

      If there is a term or criterion that hasn’t been explained clearly or if you have any further questions, please let me know.

      What Reasons Could Exclude Me from the Study?

      You cannot take part in the study if you meet any of the following conditions:

      1. Stage IV (metastatic) Triple-Negative Breast Cancer (TNBC): This means breast cancer that has spread beyond the original area to other parts of the body.
      2. History of prior invasive breast cancer: If you’ve had breast cancer that has spread into surrounding breast tissue, or evidence that cancer has returned after previous treatment.
      3. Severe or uncontrolled medical conditions: This includes systemic diseases, history of organ transplant, active bleeding diseases, ongoing or active infections, and chronic gastrointestinal conditions associated with diarrhea or previous complicated diverticulitis.
      4. Another primary malignancy: Except for certain treated skin cancers and in situ diseases which are cured and considered low-risk of recurrence.
      5. Persistent toxicities caused by previous anticancer therapy: Toxicities not improved to Grade ≤1, excluding hair loss. Some irreversible toxicities that won’t be worsened by the study may be allowed, like certain types of hearing loss.
      6. Active or prior documented autoimmune or inflammatory disorders: Conditions where the immune system attacks the body, like lupus or rheumatoid arthritis.
      7. Clinically significant corneal disease: Serious disease of the cornea, the clear outer layer at the front of your eye.
      8. Active or uncontrolled hepatitis B or C virus infection: Ongoing liver infections caused by hepatitis B or C virus.
      9. Known HIV infection that is not well controlled: Unmanaged Human Immunodeficiency Virus infection.
      10. Active tuberculosis: An ongoing infection caused by the bacterium Mycobacterium tuberculosis.
      11. Mean resting corrected QTcF > 470 ms: This refers to a measurement from an electrocardiogram that shows delayed heart electrical activity, which could indicate a risk of heart rhythm issues.
      12. Uncontrolled or significant cardiac disease: Heart conditions that are not properly managed.
      13. Non-infectious ILD/pneumonitis: Includes lung conditions that cause inflammation and scarring, such as radiation-induced conditions requiring steroids, current or suspected cases that haven’t been cleared by imaging.
      14. Severe pulmonary function compromise: Significant issues with lung function.
      15. Any known active liver disease: This refers to ongoing liver conditions.
      16. Grade ≥ 2 peripheral neuropathy: Nerve damage outside the brain or spinal cord that is moderate or severe.
      17. Prior exposure to certain PD-1/PD-L1 inhibitors: Specifically, if you’ve been treated with PD-1/PD-L1 inhibitors other than pembrolizumab.
      18. Use of immunosuppressive medication: If you have taken drugs that weaken the immune system within 14 days before randomization.
      19. Severe hypersensitivity to Dato-DXd or its components: If you are highly allergic to the investigational drug or its ingredients, including polysorbate 80 and other monoclonal antibodies.
      20. Severe hypersensitivity to PD-1/PD-L1 inhibitors: If you have a known strong allergy to PD-1/PD-L1 inhibiting drugs.
      21. Participation in another clinical study: If you’ve taken part in a clinical study with another investigational drug or device within the last 4 weeks or have previously been in a Dato-DXd, T-DXd, or durvalumab study.
      22. Pregnancy or breastfeeding: Currently pregnant, confirmed by a positive test, breastfeeding, or planning to become pregnant.

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      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      The drugs involved in the study are:

      1. Pembrolizumab (Active Substance: Pembrolizumab): An antineoplastic agent belonging to the class of immune checkpoint inhibitors. It works by blocking the programmed cell death 1 (PD-1) receptor on lymphocytes, which may directly promote antitumor immune responses.
      2. Durvalumab (Active Substance: Durvalumab): Another antineoplastic agent that is also part of the immune checkpoint inhibitors class. Durvalumab targets the programmed death-ligand 1 (PD-L1) which can be expressed by tumor cells or other cells within the tumor environment, thereby enabling the immune system to detect and attack tumors.
      3. Capecitabine (Active Substance: Capecitabine): A prodrug that is enzymatically converted to 5-fluorouracil (5-FU) in the body. As an antimetabolite antineoplastic agent, it interferes with DNA production in cells, thereby inhibiting tumor growth.
      4. Dato-DXd (Datopotamab deruxtecan, also known as DS-1062a): An experimental drug provided in the study. It is a type of antibody-drug conjugate which delivers cytotoxic drugs directly to cancer cells. Dato-DXd is designed to target a protein commonly found in cancer cells and release a chemotherapy-like drug inside those cells to destroy them.

      These active substances are used to stimulate the participants’ immune response against tumor cells or directly interfere with the tumor cell’s functions.

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

      The clinical trial involves the following active substances:

      1. Dato-DXd (Datopotamab deruxtecan, DS-1062a)

        Description: Dato-DXd is an experimental drug provided in 100mg vials and administered via IV infusion. Its efficacy and safety are being tested in this clinical trial and it is not yet widely known in medical literature as a standard of care treatment.

      2. Durvalumab (MEDI4736)

        Description: Durvalumab is an experimental drug provided in 50mg vials and given by IV infusion. It has been studied in various phases of clinical trials and is known in medical literature for treating certain types of cancer, such as urothelial carcinoma and non-small cell lung cancer.

      3. Capecitabine (XELODA®)

        Description: Capecitabine is an active comparator in tablet form used orally. It is a well-established chemotherapy medication known in medical literature and used in the treatment of various types of cancers including breast cancer.

      4. Pembrolizumab (KEYTRUDA®)

        Description: Pembrolizumab is an active comparator provided in 100mg vials for IV infusion. It is a widely known and approved immunotherapy for several types of cancer and has substantial information available in medical literature.


      Study ID

      CT-EU-00029767

      Recruitment status

      Recruting new patients

      Start of the trial

      2 years ago

      Study phase

      Phase
      III

      Diseases