罕见病药物开发面临许多挑战，罕见肿瘤学适应症也不例外。为了了解与临床药理学原理在罕见肿瘤产品开发中的应用相关的监管环境，我们回顾了 2019 年 1 月至 2023 年 3 月期间美国 FDA 批准的 39 项公开信息。目的是了解预期的临床药理学研究和知识以此类批准为基础。还审查了模型知情药物开发（MIDD）应用，因为此类方法预计将在填补罕见肿瘤学的临床药理学空白方面发挥关键作用，因为罕见肿瘤学的临床试验数量和规模可能仍然很小。研究结果强调了临床药理学如何为有效性证据、剂量优化以及影响药物行为的内在和外在因素的阐明做出贡献。在许多 NDA/BLA 中，临床药理学研究通常与建模相结合。在收到的上市后要求 (PMR) 中，18% 用于剂量优化，49% 用于 DDI，8% 用于 QTc，49% 用于特定人群，5% 用于食物效应。针对 11 种生物制剂提交的免疫原性发布了两项上市后承诺 (PMC)。 15%（39 份中的 6 份）提交的材料使用最大耐受剂量 (MTD) 将其分子推进到 2 期研究。其中 3 项获得 PMR 批准，用于剂量优化。 3  3 是最普遍的 1 期设计，在 74% 的新药申请 (NDA)/生物制品许可申请 (BLA) 审查中使用。 Rest 使用 BLRM、BOIN 或 mTPi 等创新方法，其中 BLRM 是最常见的。无缝的临床药理学和 MIDD 方法对于罕见肿瘤药物的开发至关重要。© 2023。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下公司）的独家许可。

There are many challenges with rare diseases drug development and rare oncology indications are not different. To understand the regulatory landscape as it relates to application of clinical pharmacology principles in rare oncology product development, we reviewed publicly available information of 39 approvals by US FDA between January 2019 and March 2023. The objective was to understand the expected clinical pharmacology studies and knowledge base in such approvals. Model informed drug development (MIDD) applications were also reviewed, as such approaches are expected to play a critical role in filling clinical pharmacology gaps in rare oncology, where number of clinical trials and size of these trials will perhaps continue to be small. The findings highlighted how clinical pharmacology contributed to the evidence of effectiveness, dose optimization and elucidation of intrinsic and extrinsic factors affecting drug's behavior. Clinical pharmacology studies were often integrated with modeling in many of the NDAs/BLAs. Of the post marketing requirements (PMR) received, 18% were for dose optimization, 49% for DDI, 8% for QTc, 49% for specific population, and 5% for food effect. Two post marketing commitments (PMC) were issued for immunogenicity of the 11 biologics submissions. 15% (6 of 39) of the submissions used maximum tolerated dose (MTD) to advance their molecule into Phase 2 studies. Of them 3 approvals received PMR for dose optimization. 3 + 3 was the most prevalent Phase 1 design with use in 74% of the New Drug Applications (NDA)/Biologic License Applications (BLA) reviewed. Rest used innovative approaches such as BLRM, BOIN or mTPi, with BLRM being the most common. Seamless clinical pharmacology and MIDD approaches are paramount for rare oncology drug development.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.