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    Summary
    EudraCT Number:2021-003397-32
    Sponsor's Protocol Code Number:MK2140-004
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-10-01
    Trial 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 ConcernedFrance - ANSM
    A.2EudraCT number2021-003397-32
    A.3Full title of the trial
    A Phase 2 Open-label Clinical Study to Evaluate the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Research Study, where the participant and healthcare providers are aware of the treatment being given, to evaluate safety and effectiveness of medication MK-2140 in patients with Diffuse Large B Cell Lymphoma who failed prior therapies.
    A.3.2Name or abbreviated title of the trial where available
    A Single-Cohort Study of MK-2140 in rrDLBCL
    A.4.1Sponsor's protocol code numberMK2140-004
    A.5.4Other Identifiers
    Name:INDNumber:136904
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., 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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc
    B.5.2Functional name of contact pointGlobal Clinical Trials Operations
    B.5.3 Address:
    B.5.3.1Street Address One Merck Drive P.O. Box 100
    B.5.3.2Town/ city Whitehouse Station, New Jersey
    B.5.3.3Post code 08889-0100
    B.5.3.4CountryUnited States
    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 nameZilovertamab Vedotin
    D.3.2Product code MK-2140
    D.3.4Pharmaceutical form Solution for injection
    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 INNzilovertamab vedotin
    D.3.9.1CAS number 2376463-48-6
    D.3.9.2Current sponsor codeMK-2140
    D.3.9.4EV Substance CodeSUB216408
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) Yes
    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
    Treatment of participants with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
    E.1.1.1Medical condition in easily understood language
    Diffuse Large B Cell Lymphoma (a type of non-Hodgkin’s lymphoma, in patients who failed prior therapies)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10012818
    E.1.2Term Diffuse large B-cell lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To evaluate zilovertamab vedotin with respect to objective response rate per Lugano Response Criteria as assessed by BICR
    E.2.2Secondary objectives of the trial
    1. To evaluate zilovertamab vedotin with respect to duration of response per Lugano Response Criteria as assessed by BICR
    2. To evaluate zilovertamab vedotin with respect to progression-free survival per Lugano Response Criteria as assessed by BICR
    3. To evaluate zilovertamab vedotin with respect to overall survival
    4. To evaluate the safety and tolerability of zilovertamab vedotin
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Has relapsed or refractory DLBCL and have failed at least 2 lines of prior therapy, and have failed auto-SCT or are auto-SCT ineligible. Must have received prior rituximab/anti-CD20 monoclonal antibody.
    a Relapsed disease: progression after achieving an overall response of PR or CR in response to the most recent therapy.
    b Refractory disease: failure to achieve CR or PR to the most recent therapy.
    c Ineligibility for auto-SCT:
    Is >65 years old
    Has organ dysfunction or comorbidities precluding the use of HDT or auto-SCT
    Has not responded to salvage therapy
    Has refused auto-SCT
    Has an inability to successfully collect peripheral blood stem cells
    2. Histologically confirmed diagnosis of DLBCL, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues.
    3. a. Has radiographically measurable DLBCL per the Lugano Response Criteria, with at least 1 nodal lesion (non-irradiated) that is >1.5 cm in the long axis, regardless of length of the short axis, AND/OR extranodal lesion of ≥1.0 cm in the long and short axis.
    and
    b. Has PET positive disease verified by BICR at Screening defined as 4-5 on a 5-point scale.
    4. Life expectancy of at least 3 months, in the opinion of the investigator.
    5. Is male or female, from 18 years of age inclusive, at the time of signing the informed consent.
    6. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
    • Zilovertamab vedotin: 110 days
    • Refrain from donating sperm
    PLUS either:
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent
    OR
    • Must agree to use contraception unless confirmed to be azoospermic as detailed below:
    - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
    • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
    7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Is not a WOCBP
    OR
    • Is a WOCBP and:
    - Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
    ◦ Zilovertamab Vedotin 50 days
    The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
    -Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
    - Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine and 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
    - Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
    8. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR.
    However, the participant may participate in the study without participating in FBR.
    9. Archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated has been provided.
    10. Have an ECOG performance status of 0 to 2 assessed within 7 days before time of enrollment. ECOG 2 will be capped at approximately 20%.
    11. Have adequate organ function.
    E.4Principal exclusion criteria
    1. Has received a diagnosis of PMBCL.
    2. Has undergone solid organ transplant at any time.
    3. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), serious cardiac arrhythmia requiring medication, arterial thromboembolism, cerebrovascular thromboembolism (<6 months prior to enrollment), uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mm Hg or systolic blood pressure ≥160 mm Hg) despite antihypertensive therapy; or significant conduction system ECG abnormalities, including second-degree AV block type II, third-degree AV block, or Grade ≥2 bradycardia, or serious cardiac arrhythmia requiring medication.
    4. Known history of liver cirrhosis.
    5. Has pericardial effusion or clinically significant pleural effusion.
    6. Has baseline peripheral neuropathy> Grade 1.
    7. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
    8. Has a demyelinating form of Charcot-Marie-Tooth disease.
    9. Has received prior therapy with a ROR1-directed therapy.
    10. Has contraindication to any of the study intervention components.
    11. Transformed DLBCL from indolent lymphoma.
    12. In participants with prior allo-SCT, acute GVHD or ongoing evidence of chronic GVHD manifesting as Grade ≥2 serum bilirubin, Grade ≥3 skin involvement, or Grade ≥3 diarrhea or requiring treatment for their GVHD.
    13. Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
    14. Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
    15. Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 4 weeks prior to C1D1.
    16. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
    17. Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to C1D1 or expected requirement for chronic use of a strong CYP3A4 inhibitor or inducer during Cycle 1 of study therapy
    18. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
    19. Has known active CNS lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission.
    20. Has an active infection requiring systemic therapy.
    21. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority.
    22. Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
    23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
    24. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
    Meals and Dietary Restrictions:
    Participants should avoid ingestion of grapefruit, grapefruit juice, Seville oranges, or starfruit (all of which contain CYP3A4 inhibitors) and should not use St. John’s wort (which is a potent CYP3A4 inducer).
    Otherwise, participants should maintain a normal diet unless modifications are required to manage an AE such as diarrhea, nausea, or vomiting.
    E.5 End points
    E.5.1Primary end point(s)
    1. Objective Response Rate (ORR)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 17 months
    E.5.2Secondary end point(s)
    1. Duration of Response (DOR)
    2. Progression-free Survival (PFS)
    3. Overall Survival (OS)
    4. Number of Participants Who Experience an Adverse Event (AE)
    5. Number of Participants Who Discontinue Study Treatment Due to an AE
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 72 months
    2. Up to approximately 72 months
    3. Up to approximately 72 months
    4. Up to approximately 14 months
    5. Up to approximately 11 months
    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 No
    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
    Patient reported outcome; Anti-Drug Antibody testing
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned50
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    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
    Chile
    China
    Hong Kong
    Israel
    Korea, Republic of
    New Zealand
    Puerto Rico
    Russian Federation
    South Africa
    Thailand
    Turkey
    Ukraine
    United States
    Estonia
    France
    Germany
    Ireland
    Italy
    Norway
    Poland
    Spain
    Sweden
    Switzerland
    United Kingdom
    Czechia
    Argentina
    Greece
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 100
    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)
    None
    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 Decision2021-12-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-12-21
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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