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    Summary
    EudraCT Number:2015-002552-27
    Sponsor's Protocol Code Number:B9991004
    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:2016-01-13
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2015-002552-27
    A.3Full title of the trial
    A PHASE 1B/2 OPEN-LABEL STUDY TO EVALUATE SAFETY, CLINICAL ACTIVITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB* (MSB0010718C) IN COMBINATION WITH OTHER CANCER IMMUNOTHERAPIES IN PATIENTS WITH ADVANCED MALIGNANCIES
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)
    A.3.2Name or abbreviated title of the trial where available
    JAVELIN Medley
    A.4.1Sponsor's protocol code numberB9991004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02554812
    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 SponsorPfizer Inc, 235 East 42nd Street, New York, NY 10017
    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 supportPfizer Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc.
    B.5.2Functional name of contact pointClinical Trials.gov Call Centre
    B.5.3 Address:
    B.5.3.1Street Address235 E 42nd Street
    B.5.3.2Town/ cityNew York, NY
    B.5.3.3Post code10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1800718 1021
    B.5.5Fax number+1800739 1119
    B.5.6E-mailClinicalTrials.govCallCentre@pfizer.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 nameAvelumab
    D.3.2Product code MSB0010718C
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAvelumab
    D.3.9.2Current sponsor codeMSB0010718C
    D.3.9.4EV Substance CodeSUB176547
    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) 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.IMP: 2
    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.3.2Product code PF-05082566
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.2Current sponsor codePF-05082566
    D.3.9.4EV Substance CodeSUB34231
    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 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.IMP: 3
    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.3.2Product code PF-04518600
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.2Current sponsor codePF-04518600
    D.3.9.3Other descriptive namePF-04518600
    D.3.9.4EV Substance CodeSUB168537
    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 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.IMP: 4
    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 nameanti-MCSF
    D.3.2Product code PD 0360324
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.2Current sponsor codePD 0360324
    D.3.9.3Other descriptive namePD-360,324
    D.3.9.4EV Substance CodeSUB81759
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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
    Locally advanced or metastatic solid tumors [eg, non-small cell lung cancer (NSCLC), melanoma, and squamous cell carcinoma of the head and neck (SCCHN)] triple-negative breast cancer (TNBC), or colorectal cancer (CRC)].
    E.1.1.1Medical condition in easily understood language
    Advanced cancers including non-small cell lung cancer, melanoma, and squamous cell carcinoma of the head and neck, breast cancer and colorectal cancer.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10048683
    E.1.2Term Advanced 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
     Phase 1b lead-in: To assess safety and tolerability of a single dose level of avelumab in
    combination with increasing dose levels of other immune modulators in patients with
    locally advanced or metastatic solid tumors in order to select the RP2D(s)/schedule for
    the combination.

    Phase 2: To assess objective response (OR) of avelumab in combination with other
    immune modulators in patients with locally advanced or metastatic solid tumors.
    E.2.2Secondary objectives of the trial
    To assess the overall safety and tolerability of avelumab and other immune modulators
    when given in combination;

    To characterize the PK of avelumab and other immune modulators when given in
    combination;

    To evaluate the immunogenicity of avelumab and other immune modulators when given in combination;

    To assess the antitumor activity of avelumab and other immune modulators when given
    in combination in patients with locally advanced or metastatic solid tumors;

    To assess the correlation of antitumor activity of avelumab and other immune modulators with immune biomarkers in baseline tumor tissue.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histological or cytological diagnosis of advanced/metastatic solid tumor as follows
    Measurable disease by RECIST v1.1 with at least 1 measurable lesion that has not previously been irradiated.
    Availability of tumor specimens: For Phase 1b: Archival formalin-fixed paraffin-embedded (FFPE) tissue is required if available for the first 3 patients enrolled in a cohort. For Phase 2 and additional patients enrolled beyond the first 3 in a Phase 1b cohort: FFPE tissue must be available from the most recent primary or metastatic tumor biopsy or resection prior to start of study therapy, taken within 1 year prior to study entry, with no intervening systemic anti-cancer therapy. HPV status based on locally approved testing for patients with SCCHN, and MSI status based on locally approved testing for patients with CRC.
    Patients with a history of PD-1 or PD-L1 inhibitor refractory disease (best response of PD) are not eligible.
    Combo A- 1b: NSCLC that has progressed on standard therapy or for which no standard therapy is available.
    Phase 2:
    NSCLC, melanoma, or SCCHN in any line of therapy;
    NSCLC patients with tumor ALK translocations or EGFR mutations must have received, or been refractory/intolerant to, standard therapy.
    TNBC that has progressed after 1 line of therapy or is ineligible for/intolerant to SOC; or
    SCLC that has progressed after at least 1 line of platinum-containing therapy or is ineligible for/intolerant to SOC.
    NSCLC first-line Stage IV or recurrent NSCLC that is histologically proven. Patients must not have received treatment for their metastatic or recurrent disease. Neither activating EGFR mutation nor ALK translocation/rearrangement are permitted (non-squamous cell histologies require testing if status is unknown). Patients could have received adjuvant chemotherapy or locoregional treatment that included chemotherapy for locally advanced disease as long as disease treatment occurred at least 6 months prior to study entry.
    Combo B- 1b:
    NSCLC, melanoma, or SCCHN that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
    Phase 2:
    NSCLC, melanoma, SCCHN, or microsatellite instability-high (MSIhigh) CRC in any line of therapy; or
    MSS CRC that has progressed after at least 2 lines of standard therapy or is ineligible for/intolerant to SOC.
    NSCLC patients with tumor ALK translocations or EGFR mutations must have received, or been refractory/intolerant to, standard therapy.
    Combo C- 1b:
    Ovarian cancer, SCCHN, NSCLC, or gastric cancer, that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
    MSIhigh CRC in any line of therapy;
    Phase 2 (up to 2 of the following tumor types will communicated by PACL):
    NSCLC, SCCHN, or MSIhigh CRC in any line of therapy;
    Ovarian cancer or gastric cancer that has progressed after at least 1 line of therapy or is ineligible for/intolerant to SOC; or
    MSS CRC that has progressed after at least 2 lines of standard therapy or is ineligible for/intolerant to SOC.
    NSCLC patients with tumor ALK translocations or EGFR mutations must have received or been refractory/intolerant to standard therapy.
    Combo D-1b:
    NSCLC, melanoma, or SCCHN that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC;
    MSIhigh CRC in any line of therapy;
    Bladder cancer that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
    Phase 2 (up to 2 of the following tumor types will communicated by PACL):
    NSCLC, melanoma, SCCHN, or MSIhigh CRC in any line of therapy;
    MSS CRC that has progressed after at least 2 lines of standard therapy or is ineligible for/intolerant to SOC; or
    Inoperable or metastatic transitional cell carcinoma of the bladder that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC. Other urothelial tumor types may be considered upon consultation with the Sponsor.
    NSCLC patients with tumor ALK translocations or EGFR mutations must have received or been refractory/intolerant to standard therapy.
    2. Age ≥18 years (≥20 years where applicable according to local regulation).
    3. ECOG Performance Status (PS) 0 or 1.
    4. Est. life expectancy of at least 3 months.
    5. Adequate bone marrow function (defined in protocol)
    6. Adequate renal function, with estimated creatinine clearance ≥50 mL/min
    (Phase 1b) or ≥30 mL/min (Phase 2) as calculated using the Cockcroft-Gault (CG) equation.
    7. Adequate liver function:
    a. Total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome;
    b. AST and ALT ≤2.5 x ULN, or ≤5 x ULN if there is documented metastatic disease to the liver.
    8. Resolved acute effects of any prior therapy to baseline severity or NCI CTCAE v4.03 Grade ≤1 (except alopecia and Grade ≤2 sensory neuropathy are acceptable).
    E.4Principal exclusion criteria
    Patients with any of the following characteristics/conditions will not be included in the study:
    1. Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry.
    2. Current use of immunosuppressive medication at time of randomization. Please refer to the protcol for exceptions to this criteria.
    3. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Please refer to the protcol for exceptions to this criteria.
    4. Known prior or suspected hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to mAbs (NCI CTCAE v4.03 Grade ≥3).
    5. Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 48 hours prior to study entry and there is at least 1 measurable lesion that has not been irradiated.
    6. Patients with known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry, and are neurologically stable.
    7. Previous high-dose chemotherapy requiring stem cell rescue.
    8. Prior allogeneic stem cell transplant or organ graft.
    9. 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 Class ≥II), or serious cardiac arrhythmia requiring medication.
    10. Symptomatic pulmonary embolism within 6 months prior to study entry.
    11. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) related illness.
    12. Existing periorbital edema.
    13. Hypocalcemia (serum albumin adjusted calcium <7.5 mg/dL), clinically significant bone disease that may affect safe study participation at the discretion of the investigator, or recent bone fracture (within 12 weeks prior to study entry).
    14. Active infection requiring systemic therapy.
    15. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening tests positive).
    16. Vaccination within 4 weeks of the first dose of investigational product and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
    17. Diagnosis of any other malignancy within 2 years prior to study entry, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation or castration).
    18. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study.
    19. Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation.
    20. Persisting toxicity related to prior therapy NCI CTCAE v4.03 Grade >1 (alopecia and Grade ≤2 sensory neuropathy, or other Grade ≤2 AEs not constituting a safety risk based on Investigator judgment are acceptable); previous Grade ≥3 irAE within 3 months prior to study entry; or unresolved irAEs prior to study entry.
    21. Other severe acute or chronic medical conditions, psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational products administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
    22. Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant; male patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective method(s) of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of investigational product or longer as required by local regulations.
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1b Lead-in: First 2 Cycles Dose Limiting Toxicity (DLT).
    Phase 2: Confirmed objective response (OR), as assessed by the investigator using RECIST v1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Phase 1b: First 8 weeks of treatment
    Phase 2: Baseline up to approximately 24 month
    E.5.2Secondary end point(s)
    1. AEs as characterized by type, severity (as graded by National Cancer Institute [NCI]
    Common Terminology Criteria for Adverse Events [CTCAE] v.4.03), timing,
    seriousness, and relationship to study treatments;
    2. Laboratory abnormalities as characterized by type, severity (as graded by NCI CTCAE
    v.4.03) and timing;
    3. PK parameters (Cmax and Ctrough);
    4. ADA levels;
    5. Time-to-event endpoints including Time to Tumor Response (TTR), duration of response (DR), progression-free survival (PFS) as assessed by the investigator using RECIST v1.1, and overall survival (OS);
    6. Confirmed OR during Phase 1b, as assessed by the investigator using RECIST v1.1;
    7. Biomarkers such as PD-L1 expression and tumor infiltrating CD8+ lymphocytes in
    baseline tumor tissue.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Adverse events should be documented and recorded at each visit using NCI CTCAE version 4.03.
    2. On treatment, labs to be performed prior to dosing with study treatments unless otherwise indicated
    3. PK/immunogenicity blood sampling will be collected as described in the Schedule of
    Activities for each combination.
    4. Anti-tumor activity will be assessed at 8-week intervals, and repeated at least 4 weeks after initial documentation. After 1 year from randomization or first dose ( tumor assessments will be conducted at 12-week intervals.
    5. Confirmed OR at Phase 1b: First 8 weeks of treatment
    7. Biomarkers -Baseline, End of Treatment/Withdrawal


    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 Yes
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Dose-finding
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial29
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    France
    Japan
    Netherlands
    United States
    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 trial in a Member State of the European Union (EU) is defined as the time at which it is deemed that a sufficient number of patients have been recruited and completed the study as stated in the regulatory application (ie, clinical trial application (CTA)) and ethics application in the Member State.

    End of Trial in all other participating countries is defined as Last Subject Last Visit.
    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 months4
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    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: 301
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 248
    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 state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 39
    F.4.2.2In the whole clinical trial 549
    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)
    At completion of subject's study participation, it is under the Investigator's responsibility to prescribe the most appropriate treatment and provide adequate follow up for the subject.
    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 Decision2016-01-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-14
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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