Abstract CT103: Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: Preliminary results from KEYNOTE-028

Background: The programmed death receptor 1 (PD-1) pathway is implicated in evasion of the antitumor immune response. Pembrolizumab is a potent, highly selective humanized monoclonal antibody against PD-1 designed to block interaction with its ligands, PD-L1 and PD-L2, thus removing inhibition of T-cell activation against cancer. PD-L1 is overexpressed in malignant pleural mesothelioma (MPM) and associated with poor prognosis. We assessed the safety and efficacy of pembrolizumab in patients with PD-L1-positive MPM. Methods: KEYNOTE-028 (ClinicalTrials.gov, NCT02054806) is a nonrandomized, multicohort, phase Ib trial of pembrolizumab for PD-L1-positive advanced solid tumors. Key eligibility criteria for the MPM cohort were measurable disease, PD-L1 expression in ≥1% of cells in tumor nests or PD-L1-positive bands in stroma as determined by a prototype immunohistochemistry assay at a central laboratory, failure of standard therapy, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, adequate organ function, and no autoimmune disease or interstitial lung disease. Pembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points are safety, tolerability, and preliminary efficacy. Response was assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter. Results: Of the 84 patients with MPM who were screened, 38 (45%) had PD-L1-positive tumors. Between March 2014 and December 2014, 25 patients with MPM were treated (68% men; median age, 65 years; 64% ECOG PS 1). 36% of patients had epithelioid histology. 88% of patients received ≥1 prior therapy (28% ≥2); 80% received a platinum and pemetrexed. Fifteen patients (60%) experienced a drug-related adverse event (DRAE); only 3 (12%) had grade ≥3 DRAEs. DRAEs with incidence >25% were nausea (40%), fatigue (32%), and decreased appetite (28%). Four patients (16%) experienced immune-related AEs, but only 2 patients required dose interruption (1 because of ALT increased, 1 because of uveitis). There was no treatment-related mortality, and no patients discontinued because of DRAEs. Preliminary overall response rate (confirmed and unconfirmed) was 24% (n = 6); 13 patients (52%) had stable disease, resulting in a disease control rate of 76%. Four patients (16%) had progressive disease, and 2 patients had no assessment at the time of analysis. 16 patients (64%), including all responders,