Clinical Trials /

Avelumab in First-line NSCLC (JAVELIN Lung 100)

NCT02576574

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Avelumab in First-line NSCLC (JAVELIN Lung 100)
  • 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+NSCLC

Clinical Trial IDs

  • ORG STUDY ID: EMR 100070-005
  • SECONDARY ID: 2015-001537-24
  • NCT ID: NCT02576574

Conditions

  • First Line Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AvelumabAnti-PD-L1, MSB0010718CArm A: Avelumab
PemetrexedArm B: Platinum-containing chemotherapy regimen
PaclitaxelArm B: Platinum-containing chemotherapy regimen
GemcitabineArm B: Platinum-containing chemotherapy regimen
GemcitabineArm B: Platinum-containing chemotherapy regimen
CarboplatinArm B: Platinum-containing chemotherapy regimen
CisplatinArm B: Platinum-containing chemotherapy regimen
CarboplatinArm B: Platinum-containing chemotherapy regimen
AvelumabAnti-PD-L1, MSB0010718CArm C: Avelumab

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

Trial Arms

NameTypeDescriptionInterventions
Arm A: AvelumabExperimental
  • Avelumab
Arm B: Platinum-containing chemotherapy regimenActive ComparatorPlatinum-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 milligram per meter square [mg/m^2]) +cisplatin (75 mg/m^2) or Pemetrexed (500 mg/m^2) + 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)
  • Pemetrexed
  • Paclitaxel
  • Gemcitabine
  • Gemcitabine
  • Carboplatin
  • Cisplatin
  • Carboplatin
Arm C: AvelumabExperimental
  • Avelumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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 56 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Best Overall Response (BOR) as Adjudicated by the IRC
Time Frame:Time from date of randomization up to 56 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) According to RECIST 1.1
Time Frame:Time from date of randomization up to 56 months
Safety Issue:
Description: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.
Measure:European Quality Of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire
Time Frame:Up to 56 months
Safety Issue:
Description: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).
Measure:European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status
Time Frame:Up to 56 months
Safety Issue:
Description: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.
Measure:European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)
Time Frame:Up to 56 months
Safety Issue:
Description: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 comprise 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).
Measure: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:Up to 56 months
Safety Issue:
Description: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.
Measure:Number of Subjects With Abnormalities in Safety Laboratory Tests as Graded by NCI-CTCAE (Version 4.03)
Time Frame:Up to 56 months
Safety Issue:
Description:
Measure:Number of Subjects With Abnormalities in Vital Signs, Physical Examination, and Eastern Cooperative Oncology Group (ECOG) PS.
Time Frame:Up to 56 months
Safety Issue:
Description:
Measure:Number of Subjects With Abnormalities in 12-lead ECG
Time Frame:Up to 56 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • Avelumab
  • MSB0010718C
  • Non-Small Cell Lung Cancer

Last Updated

July 6, 2021