艾昆纬-肿瘤学试验中的联合治疗剂量优化（英）

White PaperCombination Therapy Dose Optimization in Oncology Trials Design, modeling, and operational considerations for biotech and pharmaJEFFREY HODGE, MS, Vice President Early Phase Oncology, Hematology-Oncology Center of ExcellenceDAVID ALSADIUS, MD, PhD, Senior Medical Director, Solid Tumor Lead, Hematology-Oncology Center of ExcellenceJENNIFER UNDERWOOD, MSc, Senior Therapeutic Strategy Director, OncologyZHENG LIU, DSc, Director, Quantitative Clinical PharmacologyBRYCE DAVIES, MSc, Head of APAC Strategy, Early Phase Oncology and Innovative TherapiesTable of contentsIntroduction 1The growing role of combination therapies in oncology 2Dose optimization: The shift away from maximum tolerated dose 3Trial design, feasibility, and execution considerations 6Data analysis: Modeling and simulation for decision-making 10Conclusion 11References 12 iqvia.com | 1Combination therapies represent the future of oncology innovation, offering clinicians with regimens that have the potential to enhance efficacy, delay resistance and improve patients’ responses and outcomes. Yet, determining dose optimization for such regimens is among the field’s most complex challenges and requires rigorous operational and statistical planning and execution. This white paper reviews the design, operational, and analytic challenges that sponsors must consider when designing effective and efficient combination dose-finding trials. Sponsors who partner with clinical research organizations like IQVIA can leverage their experience in this setting to realize precision and efficiencies to advance combination therapies aligned with global regulatory expectations. Introduction2 | Combination Therapy Dose Optimization in Oncology TrialsThe growing role of combination therapies in oncology The combination of drugs is now central to modern oncology clinical practice, where the heterogeneity of patients’ tumors necessitates multifaceted therapeutic strategies. Figure 1 shows immunotherapies (IO), molecularly targeted small molecules, biologics, and cytotoxic chemotherapies are increasingly used together to overcome treatment resistance and enhance the durability of patient response.One of the most recent oncology regimens to receive U.S. Food and Drug Administration (FDA) approval combined the novel targeted agent inavolisib with the targeted drugs palbociclib and fulvestrant for adults with a genetically defined form of locally advanced or metastatic breast cancer following its recurrence on or after prior therapy.1,2Approvals for combination therapies have risen steadily, particularly for common cancers.3 Oncology regimens combining an experimental medicine to the existing standard of care or another novel investigational drug comprised one third of the 292 FDA drug approvals for solid tumors from 2011 to 2023.These approved combinations received indications as first-line treatments nearly twice as often as monotherapies. They were also more than twice as likely as single drugs to