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Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)

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ClinicalTrials.gov Identifier: NCT02395172
Recruitment Status : Completed
First Posted : March 20, 2015
Results First Posted : December 13, 2018
Last Update Posted : December 23, 2019
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE February 27, 2015
First Posted Date  ICMJE March 20, 2015
Results First Submitted Date  ICMJE November 20, 2018
Results First Posted Date  ICMJE December 13, 2018
Last Update Posted Date December 23, 2019
Actual Study Start Date  ICMJE March 24, 2015
Actual Primary Completion Date November 22, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
Original Primary Outcome Measures  ICMJE
 (submitted: March 19, 2015)
Overall survival time [ Time Frame: Time from 1st randomization up to 21 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
  • Overall Survival (OS) Time in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
  • Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.
  • Progression-Free Survival (PFS) Time in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.
  • Number of Participants With Confirmed Best Overall Response (BOR) in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
  • Number of Participants With Confirmed Best Overall Response (BOR) in PD-L1+ Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
  • Percentage of Participants With Objective Response in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    Percentage of participants with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
  • Percentage of Participants With Objective Response in PD-L1+ Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    Percentage of participants with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
  • Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ]
    The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score is -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest is 1.00 (no problems in all 5 dimensions).
  • Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ]
    EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
  • Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ]
    EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
  • Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ]
    EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event.
  • Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
    ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination.
  • Number of Participants With Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2015)
  • Progression-Free Survival (PFS) Time [ Time Frame: Time from 1st randomization up to 21 months ]
  • Best Overall Response (BOR) [ Time Frame: Time from 1st randomization up to 21 months ]
  • Quality of Life EuroQuol-5D Health Outcome Questionnaire [ Time Frame: Time from 1st randomization up to 21 months ]
  • Quality of Life Assessment European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status [ Time Frame: Time from 1st randomization up to 21 months ]
  • Quality Of Life Assessment EORTC Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13) [ Time Frame: Time from 1st randomization up to 21 months ]
  • Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [ Time Frame: Time from 1st randomization up to 21 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)
Official Title  ICMJE A Phase III Open-label, Multicenter Trial of Avelumab (MSB0010718C) Versus Docetaxel in Subjects With Non-small Cell Lung Cancer That Has Progressed After a Platinum-containing Doublet
Brief Summary To demonstrate superiority with regard to overall survival of avelumab versus docetaxel in participants with programmed death ligand 1 (PD-L1) positive, non-small cell lung cancer (NSCLC) after failure of a platinum-based doublet.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Avelumab
    Participants received 10 milligram per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression.
  • Drug: Docetaxel
    Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression.
Study Arms  ICMJE
  • Experimental: Avelumab
    Intervention: Drug: Avelumab
  • Active Comparator: Docetaxel
    Intervention: Drug: Docetaxel
Publications * Barlesi F, Vansteenkiste J, Spigel D, Ishii H, Garassino M, de Marinis F, Özgüroğlu M, Szczesna A, Polychronis A, Uslu R, Krzakowski M, Lee JS, Calabrò L, Arén Frontera O, Ellers-Lenz B, Bajars M, Ruisi M, Park K. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018 Nov;19(11):1468-1479. doi: 10.1016/S1470-2045(18)30673-9. Epub 2018 Sep 24. Erratum in: Lancet Oncol. 2018 Nov;19(11):e581.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 20, 2018)
792
Original Estimated Enrollment  ICMJE
 (submitted: March 19, 2015)
650
Actual Study Completion Date  ICMJE December 3, 2019
Actual Primary Completion Date November 22, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Signed written informed consent before any trial related procedure
  • Male or female participants aged greater than or equal to (>=) 18 years
  • Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment
  • Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory
  • Participants with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression
  • Participants must have progressed after an acceptable therapy defined as follows:

    1. Participants must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR
    2. Participants must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease
  • Participants with non-squamous cell NSCLC of unknown epidermal growth factor receptor (EGFR) mutation status will require testing (local laboratory, or central laboratory if local testing is not available). Participants with a tumor that harbors an activating EGFR mutation will not be eligible
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
  • Estimated life expectancy of more than 12 weeks
  • Adequate hematological function defined by White Blood Cell (WBC) count >= 2.5 × 10^9/L with absolute neutrophil count (ANC) >= 1.5 × 10^9/L, lymphocyte count >=0.5 × 10^9/L, platelet count >= 100 × 10^9/L, and hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)
  • Adequate hepatic function defined by a total bilirubin level less than or equal to (<=) 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels <= 2.5 × ULN for all participants
  • Adequate renal function defined by an estimated creatinine clearance > 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method).

Other protocol defined inclusion criteria could apply

Exclusion criteria

  • In the United States only, participants with a squamous cell histology will be excluded
  • Systemic anticancer therapy administered after disease progression during or following a platinum based combination
  • Participants with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Participants of unknown ALK and/or EGFR mutation status will require testing at screening (local laboratory, or central laboratory if local testing is not available)
  • Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4).
  • Concurrent anticancer treatment
  • Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the participant has not fully recovered from the surgery within 4 weeks of randomization
  • Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment.
  • All participants with brain metastases, except those meeting the following criteria:

    1. Brain metastases have been treated locally, and
    2. No ongoing neurological symptoms that are related to the brain localization of the disease
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

    1. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
    2. Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to (<=)10 milligram (mg) or equivalent prednisone per day
    3. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable
  • Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be <=10 mg per day of equivalent prednisone

Other protocol defined exclusion criteria could apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Chile,   Colombia,   Croatia,   Czechia,   Denmark,   France,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Peru,   Poland,   Romania,   Russian Federation,   Slovakia,   South Africa,   Spain,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Austria,   Czech Republic,   Germany,   Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02395172
Other Study ID Numbers  ICMJE 100070-004
2014-005060-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP