In response to the U.S.\ Food and Drug Administration's (FDA) Project Optimus, a paradigm shift is underway in the design of early-phase oncology trials. To accelerate drug development, seamless Phase I/II designs have gained increasing attention, along with growing interest in the efficient reuse of Phase I data. We propose a nonparametric information-borrowing method that adaptively discounts Phase I observations according to the similarity of covariate distributions between Phase I and Phase II. Similarity is quantified using a kernel-based maximum mean discrepancy (MMD) and transformed into a dose-specific weight incorporated into a power-prior framework for Phase II efficacy evaluation, such as for the objective response rate (ORR). Considering the small sample sizes typical of early-phase oncology studies, we analytically derive a confidence interval for the weight, enabling assessment of borrowing precision without resampling procedures. Simulation studies under four toxicity scenarios and five baseline-covariate settings showed that the proposed method improved the probability that the lower bound of the 95\% credible interval for ORR exceeded a prespecified threshold at efficacious doses, while avoiding false threshold crossings at weakly efficacious doses. A case study based on a metastatic pancreatic ductal adenocarcinoma trial illustrates the resulting borrowing weights and posterior estimates.

翻译：为响应美国食品药品监督管理局（FDA）的Optimus项目，早期肿瘤学试验设计正在经历范式转变。为加速药物研发，无缝I/II期设计日益受到关注，同时I期数据的高效再利用也引起广泛兴趣。本文提出一种非参数信息借用法，该方法根据I期与II期协变量分布的相似性自适应地折减I期观测数据。相似性通过基于核的最大均值差异（MMD）进行量化，并转化为剂量特异性权重，整合至用于II期疗效评估（如客观缓解率ORR）的幂先验框架中。考虑到早期肿瘤学研究通常样本量较小，我们通过解析方法推导出权重的置信区间，从而无需重抽样即可评估借用精度。在四种毒性场景与五种基线协变量设置下的模拟研究表明，所提方法能提升有效剂量处ORR的95%可信区间下限超过预设阈值的概率，同时避免在弱效剂量处出现错误的阈值跨越。基于一项转移性胰腺导管腺癌试验的案例研究展示了由此产生的借用权重与后验估计结果。