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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2020-003427-42
    Sponsor's Protocol Code Number:DS8201-A-U206
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-03-03
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2020-003427-42
    A.3Full title of the trial
    A Phase 2, multicenter, randomized study of trastuzumab deruxtecan in subjects with HER2-mutated metastatic Non-Small Cell Lung Cancer (NSCLC) [DESTINY-Lung02]
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Trastuzumab deruxtecan for subjects with HER2-mutated metastatic NSCLC
    A.3.2Name or abbreviated title of the trial where available
    [DESTINY-Lung02]
    A.4.1Sponsor's protocol code numberDS8201-A-U206
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04644237
    A.5.4Other Identifiers
    Name:IND Number:Number:137009
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorDaiichi Sankyo, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDaiichi Sankyo, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo Inc.
    B.5.2Functional name of contact pointDavid Rusnak
    B.5.3 Address:
    B.5.3.1Street Address211 Mount Airy Road
    B.5.3.2Town/ cityBasking Ridge
    B.5.3.3Post codeNJ 07920
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 908992 7876
    B.5.6E-maildrusnak@dsi.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTrastuzumab deruxtecan for injection 100 mg
    D.3.2Product code DS-8201a
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTrastuzumab deruxtecan
    D.3.9.1CAS number 1826843-81-5
    D.3.9.2Current sponsor codeDS-8201a
    D.3.9.3Other descriptive nameAnti-HER2 antibody-drug conjugate
    D.3.9.4EV Substance CodeSUB188357
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HER2-mutated metastatic Non-Small Cell Lung Cancer (NSCLC)
    E.1.1.1Medical condition in easily understood language
    Metastatic Lung Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025044
    E.1.2Term Lung cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate confirmed ORR of trastuzumab deruxtecan in human epidermal growth factor receptor 2- (HER2-) mutated NSCLC subjects treated at 5.4 and 6.4 mg/kg doses.
    E.2.2Secondary objectives of the trial
    • To evaluate the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by confirmed ORR by investigator assessment.
    • To evaluate the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by Duration of Response (DoR).
    • To evaluate further the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by Disease control rate (DCR), Progression-free survival (PFS) and Overall survival (OS).
    • To evaluate safety of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses.
    • To evaluate pharmacokinetics (PK) and immunogenicity of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses.
    • To assess symptoms, functioning and Health-related Quality of life (HRQoL) in subjects treated with trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Must have provided informed consent for study participation (see Section 10.1.2) before performance of any study-specific procedure or test.
    2. Men or women ≥18 years old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
    3. Pathologically documented metastatic NSCLC with a known activating HER2 mutation (please refer to the list of HER2 mutations, Table 10.2). The HER2 mutation must be documented from an archival or fresh tumor tissue sample analyzed by Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or equivalent laboratory performing testing to Good Laboratory Practice (GLP) standard.
    Note: HER2 mutation documented only from a liquid biopsy sample cannot be used for enrollment.
    4. Subjects who had previous treatment (2L+) including platinum therapy in the metastatic/locally advanced setting and not amenable to curative surgery or radiation. The subject must have progressed during or after the last treatment regimen or discontinued because of unacceptable toxicity.
    5. Presence of at least 1 measurable lesion confirmed by BICR based on RECIST version 1.1.
    6. Is willing and able to provide an adequate archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Resection and core needle biopsy are acceptable. Other tissue samples, eg, fine needle aspirates or cell blocks are not acceptable. For detailed instruction on tissue submission, please refer to the laboratory manual.
    7. Has ECOG PS of 0 to 1.
    8. Has LVEF ≥ 50% within 28 days before randomization.
    9. Has adequate organ function within 14 days before randomization, as defined in the protocol.
    10. Has adequate treatment washout period before randomization, as defined in the protocol.
    11. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and for 4 months for males after the last dose of study drug. Please refer protocol for more details.
    12. Male subjects must not freeze or donate sperm starting at randomization and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to randomization in this study.
    13. Female subjects must not donate, or retrieve for their own use, ova from the time of randomization and throughout the study treatment period, and for at least 7 months after the final study drug administration. Female subjects must refrain from breastfeeding hroughout this time. Preservation of ova may be considered prior to randomization in this study.
    14. Life expectancy of 3 months or more.

    Please refer to protocol for complete list of inclusion criteria.
    E.4Principal exclusion criteria
    1. Has a known driver mutation in the EGFR, BRAF, or MET exon 14 gene or a known ALK, ROS1, RET, or NTRK fusion.
    2. Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation before randomization to rule out MI.
    3. Has a corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males) based on average of the triplicate12-lead ECG at screening.
    4. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
    5. Has spinal cord compression or clinically active CNS metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study randomization.
    6. Has multiple primary malignancies within 3 years, except adequately resected non melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
    7. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
    8. Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
    9. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
    10. Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
    11. Known human immunodeficiency virus (HIV) infection. Subjects should be tested for HIV prior to randomization if required by local regulations or institutional review board (IRB)/independent ethics committee (IEC).
    12. Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C), such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1. Subjects with past or resolved hepatitis B virus (HBV) infection are eligible, if negative for hepatitis B surface antigen (HBsAg[-]) and positive for hepatitis B core antibody (anti-HBc[+]). Subjects positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
    13. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia)not yet resolved to Grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to randomization and managed with standard of care treatment) which the investigator deems related to previous nticancer therapy, such as:
    a. Chemotherapy-induced neuropathy
    b. Fatigue
    c. Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include:
    • Hypothyroidism/ hyperthyroidism
    • Type I diabetes
    • Hyperglycemia
    • Adrenal insufficiency
    • Adrenalitis
    • Skin hypopigmentation (vitiligo)
    14. Is pregnant, breastfeeding, or planning to become pregnant.
    15. Otherwise considered inappropriate for the study by the investigator.
    16. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg. pulmonary emboli within three months of the study randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.).
    17. Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
    18. Prior complete pneumonectomy.
    19. Had prior treatment with any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.
    E.5 End points
    E.5.1Primary end point(s)
    Primary efficacy endpoint is confirmed Objective Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR), assessed by blinded independent central review (BICR) based on RECIST version 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    At least 9 months after the last subject is randomized
    E.5.2Secondary end point(s)
    - Objective Response Rate
    - Duration of Response (DoR)
    - Disease Control Rate (DCR)
    - Progression-free Survival (PFS)
    - Overall Survival (OS)
    - Safety parameters (AEs, ECOG PS, vital signs, clinical laboratory parameters, ECG etc.)
    - PK endpoints: Serum concentrations of trastuzumab deruxtecan, total anti-HER2 antibody, and MAAA 1181a
    - Immunogenicity endpoint: Incidence of ADA.
    - Change from baseline in European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) and EORTC quality of life questionnaire for lung cancer trials (QLQ-LC13) scale scores
    - Time to definitive deterioration in EORTC QLQ-C30 scores
    E.5.2.1Timepoint(s) of evaluation of this end point
    ORR, DOR, PFS, OS, Safety parameters, PK, Immunogenicity, Health-related Quality of life (HRQoL): At least 9 months after the last subject is randomized
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarker Analysis, Immunogenicity, clinical pharmacology, Health economics and outcomes research (HEOR), quality of life (QoL)
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Different dose of the same IMP
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA22
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    Japan
    United States
    France
    Italy
    Netherlands
    Spain
    Korea, Republic of
    Taiwan
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    EOS will occur when the last subject’s last visit has occurred, all subjects have discontinued from the study or have died, an alternative study has become available where trastuzumab deruxtecan is offered to subjects continuing to derive benefit from such treatment, or the study is discontinued by the Sponsor for other reasons.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days26
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months7
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 135
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state11
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 66
    F.4.2.2In the whole clinical trial 150
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    An alternative study will be available to subjects who continues to derive benefit from trastuzumab deruxtecan treatment.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-03-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-16
    P. End of Trial
    P.End of Trial StatusOngoing
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