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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Avelumab; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT02395172

100070-004

2014-005060-15 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 792 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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792 participants in 2 patient groups

Avelumab

Experimental group

Treatment:

Drug: Avelumab

Docetaxel

Active Comparator group

Treatment:

Drug: Docetaxel