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    Summary
    EudraCT Number:2022-000371-39
    Sponsor's Protocol Code Number:MK-4280A-008
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-08-31
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2022-000371-39
    A.3Full title of the trial
    A Phase 3 Randomized Clinical Study of MK-4280A (coformulated favezelimab [MK-4280] plus pembrolizumab [MK-3475]) Versus Physician’s Choice Chemotherapy in PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma (KEYFORM-008)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    MK-4280A versus Physician’s Choice Chemotherapy in PD-(L)1-refractory, relapsed/refractory Classical Hodgkin Lymphoma
    A.4.1Sponsor's protocol code numberMK-4280A-008
    A.5.4Other Identifiers
    Name:INDNumber:160,067
    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 LLC
    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 LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameMK4280A (Favezelimab + Pembrolizumab)
    D.3.2Product code MK4280A
    D.3.4Pharmaceutical form 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 INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFavezelimab
    D.3.9.2Current sponsor codeMK-4280
    D.3.9.4EV Substance CodeSUB203633
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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) 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
    PD-(L)1-refractory, Relapsed or Refractory Classical Hodgkin Lymphoma
    E.1.1.1Medical condition in easily understood language
    Relapsed or Refractory Classical Hodgkin Lymphoma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10080208
    E.1.2Term Classical Hodgkin lymphoma
    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
    1. To compare MK-4280A to physician’s choice chemotherapy with respect to PFS per Lugano response criteria by BICR.
    2. To compare MK-4280A to physician’s choice chemotherapy with respect to OS.
    E.2.2Secondary objectives of the trial
    1. To compare MK-4280A to physician's choice chemotherapy with respect to OS.
    2. To evaluate MK-4280A to physician's choice chemotherapy with respect to ORR per Lugano response criteria by BICR.
    3. To evaluate MK-4280A and physician’s choice chemotherapy with respect to DOR per Lugano response criteria by BICR.
    4. To evaluate the safety and tolerability of MK-4280A.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Has histologically confirmed diagnosis of classical Hodgkin lymphoma that is FDG-avid, defined as 4-5 on a 5-point scale.
    2. Has radiographically measurable disease per the Lugano response criteria, as assessed locally by the investigator, with at least 1 nodal lesion (nonirradiated) 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.
    3. Has relapsed (defined as disease progression after most recent therapy) or refractory (defined as failure to achieve CR or PR to most recent therapy) cHL and exhausted all available treatment options with known clinical benefit, including:
    a) Have failed to achieve a response or progressed after auto-SCT, or Were unable to achieve a CR or PR to salvage chemotherapy, and therefore did not proceed to auto-SCT or were ineligible for auto-SCT due to age/comorbidities as judged by the treating physician. A minimum of 2 lines of prior therapy is required for participants who were ineligible for auto-SCT.
    b) Have relapsed after treatment with or failed to respond to BV or was ineligible for BV or who discontinued BV due to toxicity.
    4. Has progressed on treatment with an anti-PD-(L)1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies (excluding LAG-3-targeted therapies). PD-1 treatment progression is defined by meeting all of the following criteria:
    a) Received at least 3 months of therapy (with at least 2 doses) of an approved anti-PD-(L)1 mAb
    b) Documented disease progression after anti-PD-(L)1 treatment, as defined by Lugano classification.
    c) Progressive disease has been documented within 12 weeks from the last dose of anti-PD-(L)1 mAb as determined by the investigator. If disease progression was confirmed with a second scan, the initial date of disease progression documentation will be considered the date of disease progression.
    5. Is male or female, at least 18 years of age, at the time of providing informed consent.
    6. If male, agrees 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 as follows:
    - Bendamustine: 90 days
    - Gemcitabine: 90 days
    • Refrains from donating sperm
    PLUS either:
    • Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
    • Uses contraception unless confirmed to be azoospermic
    7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Not a WOCBP
    OR
    • 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. The length of time required to continue contraception for each study intervention is as follows:
    ◦ MK-4280A: 120 days
    ◦ Bendamustine: 180 days
    ◦ Gemcitabine: 180 days
    - Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours (urine) or 72 hours (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.
    - Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention (MK-4280A) or 180 days after bendamustine or gemcitabine.
    - Medical history, menstrual history, and recent sexual activity has been 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. Is eligible to receive at least one of the protocol-defined chemotherapy regimens in the opinion of the investigator in accordance with local and/or institutional guidelines.
    10. Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Archival tissue must have been collected <5 years before Screening. Details pertaining to tumor tissue submission can be found in the Laboratory Manual.
    11.Has submitted pretrial imaging.
    12. An ECOG performance status of 0 to 2 assessed within 7 days before the start of study intervention. Participants with ECOG performance status of 2 will be capped at 20%.
    13. Adequate organ function. Specimens must be collected within 7 days before the start of study intervention.
    E.4Principal exclusion criteria
    1. Has severe hypersensitivity (Grade ≥3) to pembrolizumab, favezelimab and/or any of their excipients.
    2. History of Grade ≥3 immune-related adverse event with prior checkpoint inhibitor therapy.
    3. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
    dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
    immunosuppressive therapy within 7 days before the first dose of study intervention.
    4. History of CNS metastases or active CNS involvement.
    5. Active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
    6. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
    7. Has an active infection requiring systemic therapy.
    8. History of hemophagocytic lymphohistiocytosis.
    9. Has an active seizure disorder that is not well controlled.
    10. Has clinically significant (ie, active) cardiovascular disease as follows: cerebral vascular accident/stroke (<6 months before enrollment), myocardial infarction (<6 months before enrollment), unstable angina, congestive heart failure (NYHA Class III or IV), or cardiac arrhythmia requiring medication.
    11. Received prior therapy with a LAG-3-targeted therapy.
    12. Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
    13. Received prior radiotherapy within 2 weeks of start of study intervention or radiationrelated toxicities requiring corticosteroids.
    14. Received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
    15. Has not adequately recovered from major surgical procedure or has ongoing surgical complications.
    16. Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
    17. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
    18. History of HIV infection. HIV testing is not required unless mandated by local health authority.
    19. Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
    20. History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
    21. Has had an allogeneic hematopoietic stem cell or solid organ transplantation within the last 5 years. Participants who have a transplant >5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease. Participants with a history of GvHD who have been off immunosuppressive therapy for <2 months are excluded.
    E.5 End points
    E.5.1Primary end point(s)
    1. Progression-Free Survival (PFS) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR)
    2. Overall Survival (OS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 43 months
    E.5.2Secondary end point(s)
    1. Overall Survival (OS)
    2. Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by BICR
    3. Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR
    4. Number of Participants Who Experienced At Least One Adverse Event (AE)
    5. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 105 months
    2. Up to approximately 25 months
    3. Up to approximately 43 months
    4. Up to approximately 27 months
    5. Up to approximately 24 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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarkers: PD-L1, LAG-3 IHC; RNAseq, WES, Blood for Genetic Analysis for GWAS and baseline WES
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Brazil
    China
    Israel
    Japan
    Korea, Republic of
    United States
    France
    Sweden
    Spain
    Germany
    Belgium
    Turkey
    United Kingdom
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years9
    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 years9
    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: 216
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 144
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 360
    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 Decision2022-09-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-11-23
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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