Abstract 7184: Simulating extended dosing intervals for atezolizumab: A comparative analysis between NONMEM and Pumas

Abstract The initially approved dosage regimens of 840 mg every 2 weeks, 1200 mg every 3 weeks, and 1680 mg every 4 weeks are considered excessive concerning the specified minimum effective concentration of 6 ug/mL and the significant exposure-response relationship with Adverse Events of Special Interest (AESI). Our previous research, demonstrated through simulation, indicated that an extended-interval dosing regimen (840 mg every 6 weeks) after two standard loading doses maintained efficacy with a nonsignificant exposure-response relationship with AESI.In alignment with the FDA's initiative "Project Optimus," which aims to optimize drug dosing for improved therapeutic outcomes, we explore alternative dosage regimens for atezolizumab. Through a comparison of the traditional 30-year-old industry standard NONMEM software and the recently developed PumasAI software, we simulate these regimens, utilizing our previously published article as a benchmark. Given the rapid evolution of artificial intelligence (AI) and machine learning, it is crucial for pharmacokinetic modeling to adapt and leverage these advancements. We anticipate that this paper will contribute to the integration of AI and machine learning software in pharmacokinetic analysis, aligning with the goals of "Project Optimus" to ensure that drug concentrations are optimized for efficacy and safety. Table 1: Comparative Summary of Simulated Pharmacokinetic Parameters: Pumas vs. NONMEM Pumas NONMEM Regimen Cycle Week Cmax (ug/mL) Cmax (ug/mL) Cmax (ug/mL) Cmax (ug/mL) Cmin (ug/mL) Weekly AUC (ug*day/mL) 1200 mg q3w 1st 3 384(278-533) 64.1(31.4-112) 919(640-1290) 394 (278-559) 75.6 (44.5-121) 1003 (755-1342) 7th 21 541(371-795) 146(53.8-349) 1750(977-3210) 583 (414-847) 180 (75.9-396) 2014 (1169-3535) 840 mg q2w x2, 840 mg q6w 1st 2 270(195-379) 61.6(35.5-100) 775(570-1085) 275 (184-397) 71.2 (46.4-108) 834 (620-1131) 7th 38 314(221-448) 33.6(8.8-127) 650(357-1375) 336 (235-487) 46.9 (13.5-150) 774 (441-1562) 1200 mg q3w x2, 840 mg q6w 1st 3 384(278-533) 64.1(31.4-112) 919(640-1290) 394 (278-559) 75.6 (44.5-121) 1003(755-1342) 7th 39 316(224-459) 36.0(8.4-129) 670(340-1406) 327 (217-492) 46.6 (13.4-157) 763 (411-1594) 1680 mg q4w x2, 840 mg q6w 1st 4 545(380-779) 63.1(26.9-122) 1096(735-1555) 552 (375-793) 78.1 (40.7-135) 1203(869-1651) 7th 40 318(222-469) 33.9(7.7-126) 657(343-1385) 332 (227-491) 46.5 (13.6-140) 771 (436-1464) Citation Format: Francis Bateman, Oluwatobi Arisa, Natalia Corvalan Cabanas, Yi Zeng, Cody Peer, Keith Schmidt, William Douglas Figg. Simulating extended dosing intervals for atezolizumab: A comparative analysis between NONMEM and Pumas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7184.