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J.H.M. Schellens

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    ORAL 11 - Clinical Trials 1 (ID 100)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      ORAL11.03 - Single-Agent Pembrolizumab for Patients with Malignant Pleural Mesothelioma (MPM) (ID 3011)

      10:45 - 12:15  |  Author(s): J.H.M. Schellens

      • Abstract
      • Presentation
      • Slides

      Targeting the programmed death receptor 1 (PD-1) pathway is a valid therapeutic target in a variety of solid tumors and hematologic malignancies. Pembrolizumab (MK-3475) is a potent, highly selective humanized monoclonal antibody against PD-1 and is approved in the United States for the treatment of advanced melanoma that progressed following ipilimumab and, if BRAF[V600] mutant, a BRAF inhibitor. We have previously reported preliminary antitumor response and safety data for pembrolizumab in patients with MPM enrolled in the KEYNOTE-028 study. Here we present updated safety and efficacy data, including survival, for these patients.

      KEYNOTE-028 (, NCT02054806) is a nonrandomized, multicohort phase 1b trial of pembrolizumab in patients with PD-L1–positive advanced solid tumors. Other key eligibility criteria included measurable disease, failure of standard therapy, ECOG PS 0-1, adequate organ function, and no autoimmune disease or interstitial lung disease. PD-L1 positivity was defined as expression in ≥1% of tumor cells by IHC at a central laboratory. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Response was assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end point was the ORR. Secondary end points included safety and tolerability and PFS.

      Of the 84 patients with MPM screened for PD-L1 expression, 38 (45%) patients had PD-L1–positive tumors. Of these 38 patients, 25 met the eligibility criteria and were treated with pembrolizumab. As of March 20, 2015, ORR is 28% (n = 7); 12 (48%) patients had stable disease, resulting in a disease control rate of 76%. In the 15 patients with only 1 prior line of therapy, ORR and DCR are 20% and 73%, respectively. Responses are durable, and 10 (40%) patients remain on treatment (duration, 24+ to 36+ weeks). With a median follow-up duration of 8.6 months, median PFS is 5.5 months (95% CI, 3.4-NR), and the 6-month PFS rate is 49.4%. No new safety signals were observed. 15 (60%) patients experienced a drug-related adverse event (DRAE), including 3 (12%) who experienced grade 3-4 DRAEs. Only 2 patients required dose interruption because of immune-related adverse events (transaminitis and uveitis [n = 1 each]). There was no treatment-related mortality, and no patients discontinued because of DRAEs.

      Single-agent pembrolizumab has significant clinical activity in patients with PD-L1–positive MPM. The durability of responses and the 49.4% 6-month PFS rate in this pretreated patient population warrants further investigation. Updated safety and survival data, as well as the correlation of antitumor activity with the level of PD-L1 expression, will be available at the time of presentation.

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