Abstract：
First-in-human (FIH) dose-escalation trials on oncology should prioritize safety and emphasize efficacy. We reviewed the FIH trials of 67 anti-tumor products approved by the Food and Drug Administration between 2018 and 2023 and found that the \"3 + 3\" design remains the predominant dose-escalation method (66.2%). The number of patients receiving sub-therapeutic doses is positively correlated with the maximum tolerated dose (MTD) or maximum dose (MD) to starting dose ratio (P = 0.056) and the number of dose levels in trials (P < 0.001). In addition, the proportion of products with a high ratio in antibody drugs is higher than that in small molecules (P < 0.001). The MTD or MD exceeded the label dose by three or more doses in 22.03% of the products. In conclusion, optimizing the starting dose selection method, refining the way of determining doses, and finding alternative indicators to replace toxicity as the endpoints will increase the effectiveness and broaden the beneficiary scope.
摘要：
肿瘤学首次人体（FIH）剂量递增试验应优先考虑安全性并强调有效性。我们回顾了2018年至2023年间食品药品监督管理局批准的67种抗肿瘤产品的FIH试验，发现“3+3”设计仍然是主要的剂量递增方法(66.2%)。接受亚治疗剂量的患者数量与最大耐受剂量（MTD）或最大剂量（MD）与起始剂量比（P=0.056）和试验中的剂量水平数量（P<0.001）正相关。此外,高比例产品在抗体药物中的比例高于小分子药物(P<0.001)。在22.03%的产品中,MTD或MD超过标签剂量三个或更多个剂量。总之,优化起始剂量选择方法，完善确定剂量的方法，并找到替代指标来代替毒性，因为终点将增加有效性并扩大受益范围。
