Results from KEYNOTE-021 Cohort D: a Phase 1 Study of Pembrolizumab plus Ipilimumab as Second-line Therapy for Advanced NSCLC

Conference Correspondent - ASCO 2015 - Lung Cancer

Pembrolizumab (Pembro) is a humanized anti–PD-1 monoclonal antibody. Pembro and ipilimumab (IPI), an anti–CTLA-4 antibody, have each shown activity in advanced NSCLC.a,b In melanoma, combining anti–PD-1 and anti–CTLA-4 treatment has shown robust efficacy and manageable toxicity.c On the basis of these data, Patnaik and colleaguesd reported interim results from a phase 1 study evaluating pembro + IPI in patients with recurrent NSCLC. A total of 18 patients with stage IIIB/IV NSCLC with any PD-L1 status, that had recurred after ? 2 prior regimens (including platinum doublet therapy) received pembro plus IPI every 3 weeks for 4 cycles followed by maintenance pembro. Based on emerging data from the nivolumab + IPI advanced NSCLC study,e doses were reduced from 10 mg/kg to 2 mg/kg for pembro and from 3 mg/kg to 1 mg/kg for IPI. The primary end point in this study was safety and the incidence of dose-limiting toxicities (DLTs) in the first 3 weeks of dosing. Moreover, clinical response was assessed every 6 weeks per RECIST 1.1 by investigator review.

No DLTs or dose modifications were reported for the 15 patients treated at the time of analysis. A total of 15 patients experienced drug-related AEs (DRAEs), but none led to discontinuation or death. DRAEs consisted of rash, diarrhea and vomiting, chills, cough, decreased appetite, decreased weight, dehydration, depression, dysphonia, fatigue, myalgia, pruritus, and pyrexia. Best overall responses were seen in 39% of the patients at the time of analysis, including 1 Complete Remission and 6 Partial Remissions (Table); 8 patients achieved stable disease and 3 patients demonstrated disease progression, with 71% of the patients showing a decrease in target lesion burden. These preliminary data from KEYNOTE-021 cohort D demonstrate an acceptable toxicity profile and robust antitumor activity for pembro plus IPI in patients with recurrent NSCLC.

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