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Immunogenicity of pembrolizumab (pembro) in patients (pts) with advanced melanoma (MEL) and non-small cell lung cancer (NSCLC): Pooled results from KEYNOTE-001, 002, 006, and 010.
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2016
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ImmunodeficienciesImmunologyImmunotherapeuticsImmune SystemImmunotherapyTumor ImmunityImmunochemistryAntibody EngineeringRadiation OncologyAllergyAutoimmune DiseaseMedicineImmune SurveillanceImmune FunctionAntibody ScreeningAdvanced MelanomaLung CancerNsclc Vs MelNegative Immunogenicity StatusMolecular Diagnostic TechniquesCancer ImmunosurveillanceImmune Checkpoint InhibitorMonoclonal AntibodiesOncology
3063 Background: Monoclonal antibodies (mAb) can evoke immunogenicity, leading to production of antidrug antibodies (ADA). Pembro, a humanized mAb against PD-1, has demonstrated efficacy in NSCLC and MEL. Results from NSCLC cohorts of KEYNOTE-001 (NCT01295827) and KEYNOTE-010 (NCT01905657) and from MEL cohorts of KEYNOTE-001, KEYNOTE-002 (NCT01704287), and KEYNOTE-006 (NCT01866319) are presented. Methods: Samples were analyzed for antipembro antibodies using electrochemiluminescence immunoassay methodology following a standard 3-tiered assay approach consisting of screening, confirmatory, and antibody titer assessment. Screening positives were tested in a confirmatory assay checking specificity of signal for pembro. In confirmed positive samples Ab titer, neutralizing capacity, drug exposure, efficacy, and AEs were assessed. The immunogenicity approach classified ADA samples as positive, negative, or inconclusive. Overall immunogenicity incidence was defined as proportion of treatment-emergent (TE) positive pts to the number of evaluable pts with a confirmed TE, non–TE-positive or negative immunogenicity status. Negative immunogenicity status was confirmed if ADA results of the pretreatment and postdose samples were negative in the confirmatory assay, and the pembro concentration was below the drug tolerance level in the last postdose sample. Results: Across cohorts, 2910 pts provided 11,886 pretreatment and posttreatment serum samples. Overall, 2632 pts (n = 1535 MEL, n = 1097 NSCLC) were included in the immunogenicity analysis. False-positive rates were 2.7% and 2.8% with Intertek and PPD assays, respectively. Of the 1087 (41%) evaluable pts, 19 (1.7%) had a TE-positive ADA, 10 (0.9%) were non–TE-positive, and 1058 (97.3%) had negative immunogenicity status. Initial results indicate a higher incidence rate in NSCLC vs MEL (2.5% vs 0.7%). In pts with a TE-positive ADA, no impact of antipembro antibodies on drug exposure, safety, or efficacy was observed. Conclusions: Pembro has a low potential to elicit the formation of ADA, and if ADA formation occurs, it has been shown to have no clinically relevant impact. Clinical trial information: NCT01295827, NCT01905657, NCT01704287, NCT01866319.