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B. Piperdi



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    ORAL 10 - SCLC (ID 98)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      ORAL10.04 - Pembrolizumab for ED SCLC: Efficacy and Relationship with PD-L1 Expression (ID 3285)

      10:45 - 12:15  |  Author(s): B. Piperdi

      • Abstract
      • Presentation
      • Slides

      Background:
      Patients with extensive-stage disease (ED) small cell lung cancer (SCLC) have limited treatment options and poor survival following failure of platinum-based chemotherapy. Pembrolizumab, a humanized IgG4 monoclonal antibody against PD-1 designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2, has demonstrated robust antitumor activity and a manageable toxicity profile in several advanced cancers, including NSCLC. We assessed the safety and efficacy of pembrolizumab in patients with PD-L1–positive SCLC in the ongoing, multicohort, phase 1b KEYNOTE-028 study (ClinicalTrials.gov, NCT02054806).

      Methods:
      Key eligibility criteria for the SCLC cohort include failure of or inability to receive standard therapy, ≥1 measurable lesion per RECIST v1.1, ECOG performance status 0 or 1, PD-L1 expression in ≥1% of cells in tumor nests or PD-L1–positive bands in stroma as assessed by IHC using the 22C3 antibody at a central laboratory, no autoimmune disease, no interstitial lung disease, and no prior anti–PD-1 or anti–PD-L1 therapy. Pembrolizumab is given at 10 mg/kg every 2 weeks for 24 months or disease progression, intolerable toxicity, or investigator decision. Patients with progressive disease who are clinically stable may continue treatment until confirmation of progression 4 weeks later. Response will be assessed per RECIST v1.1 by investigator review every 8 weeks for the first 6 months, then every 12 weeks thereafter. Adverse events (AEs), including potentially immune-related adverse events, will be collected throughout the study and for 30 days (90 days for serious AEs) thereafter. Primary end points are safety and tolerability and the overall response rate. The relationship between pembrolizumab antitumor activity and potential biomarkers, including the level of PD-L1 expression, is an exploratory end point.

      Results:
      Of the 147 patients with SCLC who had evaluable tumor samples and were screened for PD-L1 expression, 42 (29%) had PD-L1–positive tumors. Overall, 24 patients with SCLC were enrolled and received ≥1 pembrolizumab dose. Among the 20 patients treated as of March 13, 2015, median age was 59.5 years, 55% were men, and 75% had an ECOG performance status of 1. All patients had received prior chemotherapy with a platinum + etoposide.

      Conclusion:
      Analyses of safety and tolerability and response are ongoing, as are analyses on the relationship between the level of PD-L1 expression and pembrolizumab response. These data will be available for presentation.

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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): B. Piperdi

      • Abstract
      • Presentation
      • Slides

      Background:
      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.

      Methods:
      KEYNOTE-028 (ClinicalTrials.gov, 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.

      Results:
      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.

      Conclusion:
      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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