MK-3475 in Combination With Docetaxel vs Docetaxel Alone in Non-Small Cell Lung Cancer Patients
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a phase II open-label randomized clinical trial of MK-3475 (Pembrolizumab) on
      previously treated non-small cell lung cancer (NSCLC) patients . This drug has shown to allow
      partial response according to the immune-related response criteria and the response
      evaluation criteria in solid tumors (RECIST). The main endpoint is to compare the overall
      response rate (ORR) of MK-3475 with docetaxel or docetaxel alone in patients with advanced
      NSCLC.
    

Detailed description: 
      MK-3475 (MK-3475) is an IgG4 monoclonal antibody to PD1, which received a 'breakthrough
      therapy' designation for advanced melanoma from the FDA in January 2013. Preliminary results
      from the NSCLC cohort of a phase I dose expansion trial of MK-3475 were presented at the 2013
      World Conference on Lung Cancer meeting. MK-3475 was administered intravenously every three
      weeks, and continued until disease progression based upon immune related response criteria
      (irRC) or unacceptable toxicity. IrRC take into account the potential for different patterns
      of response that can be seen with immunotherapy. Of the 38 patients with previously treated
      advanced NSCLC evaluable for efficacy, 9 (24 percent) achieved at least partial response by
      irRC. Standard oncology criteria for response (Response Evaluation Criteria In Solid Tumors,
      RECIST were available for 33 of these patients, with at least a partial response in seven
      patients (21 percent). Median overall survival was 51 weeks. Therapy was well tolerated, with
      one case of pneumonitis (grade 2) and one case of pulmonary edema (grade 3) reported. Tumor
      PDL1 expression (assessed with a different assay than that used for the trials evaluating
      Nivolumab and MPDL3280A; antibody used undisclosed) was available for 33 of the patients who
      had irRC assessments and 29 of those with standard oncology (RECIST) assessment. Of the 9
      patients with PDL1 positivity and irRC response data, 6 achieved at least partial response
      (67 percent); of the 7 patients with PDL1 positivity and standard oncology response data, 4
      achieved response (57 percent). Of note, 1 of 24 patients with PDL1 negativity achieved
      response by irRC; 2 of 22 patients with PDL1 negativity had response by standard oncology
      criteria (RECIST).

      Based upon these results, a randomized phase II trial comparing MK-3475 to standard salvage
      docetaxel in patients with advanced NSCLC has been launched (NCT01905657), however there is
      no study in which the synergistic activity of Docetaxel + MK-3475 were evaluated, this could
      open the possibility of using this drug concurrently with Docetaxel as standard therapy in
      patients with progression of the disease despite a double platinum-based regimen.

      Measure the expression levels of PD1/PD-L1/PD-L2 subpopulations tumor cells of patients with
      NSCLC who come to the clinic of the National Cancer Institute and relevant way, associating
      their role forecast and its potential as a biomarker, relating the PD-L1 levels with
      clinicopathologic characteristics of the patients studied.
    

Intervention name(s): MK-3475; Docetaxel
Intervention type(s): Drug; Drug
Intervention description(s): The dosing interval of pembrolizumab can be increased in case of toxicity.; Use on both arms as standard of care.
Other intervention name(s): pembrolizumab; taxotere
Intervention MeSH terms: Docetaxel; Pembrolizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients will be randomly assigned (1:1) using a random numbers table to receive either monotherapy Docetaxel for 6 cycles or Pembrolizuymab plus Docetaxel for 6 cycles, following with maintenance therapy with Pembrolizumab until disease progression or unacceptable toxicity.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: PDL1; monoclonal antibody