Abstract C038: Impact of assessment schedules on atezolizumab anti-drug antibody incidence rates

Abstract Background Anti-Drug Antibodies (ADA) have been of increasing interest with the rise of immunotherapy treatment. Regulatory guidance recommends sponsors assess ADA during product development studies, including ADA incidence and the effect of ADA on efficacy, safety, and PK. They also caution against comparing ADA incidence between products. Recent literature described the effect of assessment schedules and other factors on incidence rates of ADA. Here we show the impact of different assessment schedules. Methods We computed atezolizumab ADA incidence rates for 8 atezolizumab Phase III studies modeling reduced ADA assessment schedules. Atezolizumab studies included OAK, IMpower130, IMpower150, IMpower110, IMpower010, IMpower133, IMbrave150, IMspire150. All studies administered Q3W, and all but 3 of the studies collected ADA samples at Cycle (C) 1, 2, 3, 4, 8, 16, 24, 32, end of treatment and washout. Reduced ADA assessment schedules were chosen from publicly available ADA assessment schedules of other immune checkpoint inhibitors. Chosen schedules included assessments C 1,4 plus washout, similar to durvalumab ADA collection, and C 1, 2, 4, 8, 16, 24, 32, end of treatment plus washout, similar to nivolumab ADA collection. Results The calculated ADA incidence rates, computed assuming reduced ADA assessment schedules, were decreased across all atezolizumab studies, irrespective of the alternative incidence calculation schedule employed. When incidences were calculated using the most reduced ADA assessment schedule (C1, C4, washout), similar to durvalumab's collection, the rate for atezolizumab ADA decreased significantly, reaching a low of 2.5%. For example, the ADA rate in IMpower133 decreased from18.6% to 2.5% , and in IMpower010 from 30.4% to 15.5%. Across all eight studies, the computed incidence range decreased from 13.3%--36.4% to 2.5%--15.5%. Similarly, when an alternative schedule similar to nivolumab ADA collection schedule was used the ADA incidence rate for atezolizumab in IMpower130 decreased from 22.9% to 19.2%, and in IMspire150 from 13.3% to 13.0%. The computed incidence range across 8 studies decreased to 13.0%--34.7%. Conclusions When reduced assessment schedules are used, transient ADA are less likely to be measured, resulting in a lower reported ADA rate. Conversely, frequent ADA sampling may result in an ADA incidence rate including positive transient cases that have little or no clinical significance. Our results highlight why ADA incidence should not be compared between different products. Citation Format: Richard S. Finn, Coen A. Bernaards, Steven J. Swanson, Barbara Gitlitz, Lily J. Nguyen, James Zanghi, Sophie Cousin. Impact of assessment schedules on atezolizumab anti-drug antibody incidence rates [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C038.