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Avelumab in First-line Non-Small Cell Lung Cancer (JAVELIN Lung 100)

This study is currently recruiting participants.
Verified October 2017 by EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02576574
First Posted: October 15, 2015
Last Update Posted: October 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
  Purpose
The purpose of this study is to demonstrate superiority with regard to Overall Survival (OS) or Progression Free Survival (PFS) of avelumab versus platinum-based doublet, based on an Independent Review Committee assessment, in Non-small cell lung cancer (NSCLC) subjects with Programmed death ligand 1+ (PD-L1+) tumors

Condition Intervention Phase
First Line Non-Small Cell Lung Cancer Drug: Avelumab Drug: Pemetrexed Drug: Paclitaxel Drug: Gemcitabine Drug: Carboplatin Drug: Cisplatin Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open-label, Multicenter Trial of Avelumab (MSB0010718C) Versus Platinum-based Doublet as a First-line Treatment of Recurrent or Stage IV PD-L1+ Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Primary Outcome Measures:
  • Progression Free Survival (PFS) in Subjects With High PD-L1 + Tumor Expression Based on an Independent Review Committee (IRC) Assessment According to RECIST 1.1 [ Time Frame: Time from date of randomization until PD or death, assessed up to 39 months ]
    PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) as determined by the independent review committee or death due to any cause in the absence of documented PD, whichever occurs first.

  • Overall Survival (OS) in Subjects With High PD-L1 + Tumor Expression [ Time Frame: Time from date of randomization until death, assessed up to 49 months ]
    The OS is defined as the time from randomization to the date of death, regardless of the actual cause of the subjects' death.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) in Subjects With Moderate and High PD-L1 + Tumor Expression Based on an IRC Assessment According to RECIST 1.1 [ Time Frame: Time from date of randomization until PD or death, assessed up to 39 months ]
    PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) as determined by the independent review committee or death due to any cause in the absence of documented PD, whichever occurs first.

  • Overall Survival (OS) in Subjects With Moderate and High and any PD-L1 + Tumor Expression [ Time Frame: Time from date of randomization until death, assessed up to 49 months ]
    The OS is defined as the time from randomization to the date of death, regardless of the actual cause of the subjects death.

  • Best Overall Response (BOR) as Adjudicated by the IRC [ Time Frame: Time from date of randomization up to 39 months ]
    BOR will be determined according to RECIST 1.1. 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. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR.

  • Duration of Response (DOR) According to RECIST 1.1 [ Time Frame: Time from date of randomization up to 39 months ]
    DOR will be determined according to RECIST 1.1, defined for each subject with a confirmed response as the time from the date of the first assessment demonstrating a CR or PR to date of the first assessment demonstrating PD or death within 12 weeks after the last tumor assessment, whichever occurs first. 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. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire [ Time Frame: Baseline up to 49 months ]
    The EQ-5D-5L Health Outcome Questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defines 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 using a one to one matching. 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 Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status [ Time Frame: Baseline up to 49 months ]
    EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer subjects. It consists 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 ranges from 0 to 100; High score indicates 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) [ Time Frame: Baseline up to 49 months ]
    EORTC QLQ-LC13 consists of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprises 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, and medicine for pain). 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 Subjects With Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug administration ]
    TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration and 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.

  • Number of Subjects With Abnormalities in Safety Laboratory Tests as Graded by NCI-CTCAE (Version 4.03) [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug administration ]
  • Number of Subjects With Abnormalities in Vital Signs, Physical Examination, and Eastern Cooperative Oncology Group (ECOG) PS. [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug administration ]
  • Number of Subjects With Abnormalities in 12-lead ECG [ Time Frame: Screening and at the End-of-Treatment visit ]

Estimated Enrollment: 1095
Actual Study Start Date: October 29, 2015
Estimated Study Completion Date: July 26, 2024
Estimated Primary Completion Date: July 25, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Avelumab Drug: Avelumab
Subjects will be administered with avelumab at a dose of 10 milligram per kilogram (mg/kg) 1-hour intravenous (IV) infusion once every 2 weeks until disease progression or unacceptable toxicities.
Other Names:
  • Anti-PD-L1
  • MSB0010718C
Active Comparator: Arm B: Platinum-containing chemotherapy regimen

Platinum-containing chemotherapy regimen: Investigator's choice platinum containing chemotherapy regimen to be administered consisting of one of the following:

Non-squamous tumor histology

Pemetrexed (500 mg/m^2) +cisplatin (75 mg/m^2) or carboplatin (AUC 6 mg/mL*min)

Squamous tumor histology

Paclitaxel (200 mg/m^2) +carboplatin (AUC 6 mg/mL*min)

Gemcitabine (1250 mg/m^2)+ cisplatin (75 mg/m^2)

Gemcitabine (1000 mg/m^2 )+carboplatin (AUC 5 mg/mL*min)

Drug: Pemetrexed
Pemetrexed 500 mg per square meter (mg/m^2) by IV infusion on Day 1 of 3-Week cycle up to a maximum of 6 cycles of IV injection until disease progression or unacceptable toxicities.
Drug: Paclitaxel
Paclitaxel 200 mg/m^2 by IV infusion on Day 1 of 3-Week cycle up to a maximum of 6 cycles of IV injection until disease progression or unacceptable toxicities.
Drug: Gemcitabine
Gemcitabine 1250 mg/m^2 on Day 1 and Day 8 by IV infusion in 3-Week cycle up to a maximum of 6 cycles when combined with cisplatin of IV injection until disease progression or unacceptable toxicities.
Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 on Day 1 and Day 8 by IV infusion in 3-Week cycle up to a maximum of 6 cycles of IV injection when combined with carboplatin until disease progression or unacceptable toxicities.
Drug: Carboplatin
Carboplatin AUC 5 mg/mL*min in 3-Week cycle up to a maximum of 6 cycles of IV injection when combined with gemcitabine until disease progression or unacceptable toxicities.
Drug: Cisplatin
Cisplatin 75 mg/m^2 by IV infusion in 3-Week cycle up to a maximum of 6 cycles of IV injection until disease progression or unacceptable toxicities.
Drug: Carboplatin
Carboplatin AUC 6 mg/mL*min by IV infusion in 3-Week cycle up to a maximum of 6 cycles of IV injection when combined with pemetrexed, or paclitaxel until disease progression or unacceptable toxicities.
Experimental: Arm C: Avelumab Drug: Avelumab
Subjects will be administered with avelumab at a dose of 10 milligram per kilogram (mg/kg) 1-hour intravenous (IV) infusion once a week for 12 weeks and then once every 2 weeks until disease progression or unacceptable toxicities.
Other Names:
  • Anti-PD-L1
  • MSB0010718C

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged greater than or equal to (>=) 18 years
  • With Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
  • At least 1 measurable tumor lesion
  • With histologically confirmed metastatic or recurrent (Stage IV) non-small cell lung cancer (NSCLC)
  • With availability of a recently-obtained, formalin-fixed, paraffin-embedded (FFPE) tissue sample containing tumor (biopsy from a non-irradiated area preferably within 6 months) or a minimum number of 10 (preferably 25) unstained tumor slides cut within 1 week, and suitable for PD-L1 expression assessment
  • Subjects must not have received any treatment for systemic lung cancer, and have an estimated life expectancy of more than 12 weeks
  • Other protocol defined criteria could apply

Exclusion Criteria:

  • Subjects whose disease harbors a EGFR mutation, or anaplastic lymphoma kinase (ALK) rearrangement are not eligible.
  • Other exclusion criteria include prior therapy with any antibody or drug targeting T cell coregulatory proteins, concurrent anticancer treatment, or immunosuppressive agents
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade >= 3 NCI CTCAE v 4.03), history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma), and persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v 4.03.
  • Subjects with brain metastases are excluded, except those meeting the following criteria: brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to randomization, subjects must be either off steroids or on a stable or decreasing dose of <= 10 mg daily prednisone (or equivalent), and do not have ongoing neurological symptoms that are related to the brain localization of the disease.
  • Other protocol defined criteria could apply
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02576574


Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center 49 6151 72 5200 service@merckgroup.com

  Show 247 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02576574     History of Changes
Other Study ID Numbers: EMR 100070-005
2015-001537-24 ( EudraCT Number )
First Submitted: October 13, 2015
First Posted: October 15, 2015
Last Update Posted: October 31, 2017
Last Verified: October 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Avelumab
MSB0010718C
Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors