Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Avelumab; Docetaxel
Intervention description: Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.; Participants received 75 mg per square meter (m^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Intervention MeSH terms: Docetaxel; Avelumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 792.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avelumab; MSB0010718C; Non-Small Cell Lung Cancer; Anti-PD-L1

Summary:

      The main purpose of this study was 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.
    

Eligibility criteria:

        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