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    Summary
    EudraCT Number:2021-006046-12
    Sponsor's Protocol Code Number:011121
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-11-15
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2021-006046-12
    A.3Full title of the trial
    Efficacy of immunotherapy in patients with MMR-deficient localized colon cancer scheduled for curative surgery
    - A prospective, phase II study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficay of immunotherapy berfore surgery for localized dMMR colon cancer
    Effekt af immunterapi før operation for tyktarmskræft af typen dMMR uden spredning
    A.3.2Name or abbreviated title of the trial where available
    Reset
    A.4.1Sponsor's protocol code number011121
    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 SponsorRigshospitalet
    B.1.3.4CountryDenmark
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportThe departments of the participating hospitals.
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationZealand University Hospital
    B.5.2Functional name of contact pointCenter for Surgical Science
    B.5.3 Address:
    B.5.3.1Street AddressLykkebækvej 1
    B.5.3.2Town/ cityKøge
    B.5.3.3Post code4600
    B.5.3.4CountryDenmark
    B.5.6E-mailtoju@regionsjaelland.dk
    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 Yes
    D.2.1.1.1Trade name Keytruda®
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    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.3.4Pharmaceutical form 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 INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number400
    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
    Patients with early stage (stage I-III) dMMR colon cancer
    Patienter med stadium I-III dMMR colon cancer
    E.1.1.1Medical condition in easily understood language
    Patients with colon cancer, that has not spread to other organs and are of the subtype dMMR (deficient mismatch repair).
    Patienter med colon cancer, der ikke har spredt sig til andre organer og er af typen dMMR.
    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 LLT
    E.1.2Classification code 10009951
    E.1.2Term Colon cancer NOS
    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
    The main objective of this study is to evaluate the efficacy of neoadjuvant treatment with pembrolizumab before colonic resection in patients with early-stage (I-III) dMMR colon cancer.
    E.2.2Secondary objectives of the trial
    The secondary objectives include investigating the safety and tolerability of pembrolizumab administered before surgery and developing predictive biomarkers that can identify patients with a pathological complete response to pembrolizumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Have histologically confirmed localized dMMR stage cT1N0M0 to cT4N2M0 (stage I to III) colon carcinoma.
    • Have indication for elective curative intended surgery without neoadjuvant chemo-therapy.
    • Be ≥ 18 years of age on the date of signing the informed consent.
    • Provide written informed consent prior to registration according to the local regula-tory requirements.
    • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    Have adequate bone marrow function:
    o Hemoglobin ≥ 6.2 mmol/L or ≥ 10 g/dL
    o Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
    o Platelet count ≥ 100 × 109/L
    Have adequate kidney function:
    o Glomerular filtration rate (GFR) ≥ 60 mL/min or creatinine ≤1.5 X upper lim-it of normal (ULN)
    Have adequate liver function:
    o Total bilirubin ≤ 1.5 × ULN
    o Alanine aminotransferase (ALT): 10–70 U/L for males and 10–45 U/L for fe-males or ≤ 2.5 × ULN
    o Alkaline phosphatase: 35–105 U/L or ≤ 2.5 × ULN
    E.4Principal exclusion criteria
    • Has any serious or uncontrolled medical disorder that, in the opinion of the investi-gator or treating physician, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
    • Has an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus).
    • Has received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody/drug specifically targeting the T-cell co-stimulation or checkpoint pathways.
    • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active chronic or acute Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected).
    • Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoim-mune disease.
    • Has a history of allergy to study drug components or a history of severe hypersensi-tivity reaction to any monoclonal antibody
    E.5 End points
    E.5.1Primary end point(s)
    • Number of patients with pathological complete response.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluation after surgery with resection of the tumor.
    E.5.2Secondary end point(s)
    • Safety and tolerability of pembrolizumab administered before surgery. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received pembrolizumab using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded. AEs will be analyzed including but not limited to all AEs, SAEs, fatal AEs, and laboratory changes.
    • Postoperative surgical complications determined by Clavien-Dindo classification system.
    • Number of patients with major pathological response to treatment, corresponding to Mandard tumor regression grade 1 (complete response) or 2 (near complete response).
    • Number of patients with clinical complete response
    • Overall survival. Defined as the time from inclusion to death due to any cause.
    • Disease-free survival. Defined as the time from inclusion to recurrence or death due to any cause.
    • Response evaluation at the pre-operative MDT meeting
    • Biomarker assessment including the comparison of immunological markers across pre- and post-treatment biopsies and sequential blood samples using nCounter and GeoMx platforms (NanoString technologies, USA).
    • Methylated circulating cell-free DNA (cfDNA) specific for colon cancer analyzed across sequential blood samples using the TriMeth test.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Analyses on blood and tissue samples will be done in bulk, when the samples have been collected.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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 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 concerned10
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    End of study according to primary endpoint (Number of patients with pathological complete response), as recommended by the GCP Unit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned 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: 42
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 43
    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 state85
    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 Decision2021-12-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-07-06
    P. End of Trial
    P.End of Trial StatusOngoing
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