{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:02:58Z","timestamp":1784955778186,"version":"3.55.0"},"reference-count":172,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pediatric oncology drug development remains uniquely challenging due to the rarity and biological heterogeneity of childhood cancers, ethical considerations in trial conduct, and the limited feasibility of large, randomized studies. Despite these barriers, recent years have seen a notable acceleration in the approval of oncology therapies for pediatric populations, driven by advances in molecularly targeted treatments, evolving regulatory requirements, and innovation in trial design. Reducing nonclinical data requirements and increasing the adaptation of model\u2011informed drug development approaches are also contributing to advances in pediatric oncology treatment by supporting dose selection, optimizing study design, and reducing unnecessary patient burden. In this review, recent regulatory requirements from the United States, the EU, and other key regions on pediatric oncology drug development are discussed. Thirty\u2010three drugs with oncology indications in pediatric populations approved by the US FDA between 2018 and 2025 are reviewed. These approvals provide examples of how nonclinical and clinical data were generated with a focus on strategies for dose\u2010finding and justification. Common challenges and considerations related to clinical operations and formulation development in pediatric populations and the emerging use of real\u2010world data, external controls, and artificial intelligence\/machine learning are also discussed.<\/jats:p>","DOI":"10.1002\/jcph.70242","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:01:06Z","timestamp":1784901666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accelerating Pediatric Oncology Drug Development: Advances in Clinical Pharmacology, Trial Design, Non\u2010Clinical Evidence, and Regulatory Science"],"prefix":"10.1002","volume":"66","author":[{"given":"Ya\u2010Feng","family":"Wen","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarandeep","family":"Boyanapalli","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Anderson","sequence":"additional","affiliation":[{"name":"Regulatory Affairs Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao","family":"Dang","sequence":"additional","affiliation":[{"name":"Clinical Development Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan","family":"Xing","sequence":"additional","affiliation":[{"name":"Biostatistics Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Calvet","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Hart","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreeneeranj","family":"Kasichayanula","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_2_16_2_1","unstructured":"American Association for Cancer Research\u00ae.AACR Pediatric Cancer Progress Report.2025. Accessed April 4 2026.https:\/\/cancerprogressreport.aacr.org\/wp\u2010content\/uploads\/sites\/2\/2025\/12\/AACR_PCPR_2025.pdf"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5pm00090d"},{"key":"e_1_2_16_4_1","unstructured":"National Comprehensive Cancer Network (NCCN).NCCN Guidelines on Pediatric Acute Lymphoblastic Leukemia Version 1.2026. Accessed March 16 2026.https:\/\/www.nccn.org\/guidelines\/guidelines\u2010detail?category=1&id=1496"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30585"},{"key":"e_1_2_16_6_1","unstructured":"American Cancer Society (ACS).Cancer Facts & Figures.2026. Accessed March 16 2026.https:\/\/www.cancer.org\/content\/dam\/cancer\u2010org\/research\/cancer\u2010facts\u2010and\u2010statistics\/annual\u2010cancer\u2010facts\u2010and\u2010figures\/2026\/2026\u2010cancer\u2010facts\u2010and\u2010figures.pdf"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27809"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcped.2023.100005"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2024\u2010066920"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272\u2010021\u201000455\u20101"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1359"},{"key":"e_1_2_16_12_1","unstructured":"YERVOY\u00ae US prescribing information (USPI ipilimumab) injection for intravenous use Ref ID: 5595665.FDA Center for Drug Evaluation and Research. ;2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/125377s136lbl.pdf"},{"key":"e_1_2_16_13_1","unstructured":"OPDIVO\u00ae US prescribing information (USPI nivolumab) injection for intravenous use Ref ID: 5767070.FDA Center for Drug Evaluation and Research;2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2026\/125554s135lbl.pdf"},{"key":"e_1_2_16_14_1","unstructured":"NDA\/BLA.Multidisciplinary review and evaluation opdualag (nivolumab and relatlimab\u2010rmbw) BLA 761234 Ref ID: 4955210. FDA Center For Drug Evaluation and Research;2022.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2022\/761234Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_15_1","unstructured":"KEYTRUDA\u00ae\u00ae US prescribing information (USPI pembrolizumab) injection for intravenous use.FDA Center for Drug Evaluation and Research.2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2026\/125514Orig1s186lbl.pdf"},{"key":"e_1_2_16_16_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa\u2010pmph) BLA 761467 Ref ID: 5662067.FDA Center For Drug Evaluation and Research.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2025\/761467Orig1 Orig2s000MultidisciplineR.pdf"},{"key":"e_1_2_16_17_1","unstructured":"LUTATHERA\u00ae US prescribing information (USPI lutetium Lu 177 dotatate) injection for intravenous use.FDA Center for Drug Evaluation and Research.2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/208700Orig1s032lbl.pdf"},{"key":"e_1_2_16_18_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation AZEDRA (131I\u2010Iobenguane) NDA 209607 Ref ID: 4297867.FDA Center For Drug Evaluation and Research.2018.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/209607Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_19_1","unstructured":"WELIREG\u00ae US prescribing information (USPI belzutifan) tablets for oral use Ref ID: 5590635.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/215383s012lbl.pdf"},{"key":"e_1_2_16_20_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation TAZVERIK (tazemetostat) NDA 211723 Ref ID: 4550626.FDA Center For Drug Evaluation and Research.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/211723Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_21_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation VORANIGO (vorasidenib) NDA 218784 Ref ID: 5425021.FDA Center For Drug Evaluation and Research.2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/218784Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_22_1","unstructured":"CABOMETYX\u00ae US prescribing information (USPI cabozantinib) tablets for oral use Ref ID: 5675022.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/208692s019lbl.pdf"},{"key":"e_1_2_16_23_1","unstructured":"ADCETRIS\u00ae US prescribing information (USPI brentuximab vedotin) for injection for intravenous use.FDA Center for Drug Evaluation and Research. Ref ID: 5529733.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/125388Orig1s108lbl.pdf"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1682"},{"key":"e_1_2_16_25_1","unstructured":"TECENTRIQ\u00ae US prescribing information (USPI atezolizumab) injection for intravenous use Ref ID: 5696312.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/761034s059lbl.pdf"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425\u2010019\u20100791\u2010x"},{"key":"e_1_2_16_27_1","unstructured":"Office of Clinical Pharmacology Review ELZONRIS (Tagraxofusp) BLA 761116 Ref ID: 4352982.FDA Center For Drug Evaluation and Research.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/761116Orig1s000ClinPharmR.pdf"},{"key":"e_1_2_16_28_1","unstructured":"RETEVMO\u00ae US prescribing information (USPI selpercatinib) capsules or tablets for oral use Ref ID: 5699109.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/213246s015s016 218160s005s006lbl.pdf"},{"key":"e_1_2_16_29_1","unstructured":"NDA multidisciplinary review and evaluation RETEVMO (selpercatinib) NDA 213246 Ref ID: 4604998.FDA Center For Drug Evaluation and Research.2020.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/213246Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_30_1","unstructured":"MYLOTARGTM US prescribing information (USPI gemtuzumab ozogamicin) injection for intravenous use Ref ID: 4625634.FDA Center for Drug Evaluation and Research.2020.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/761060s004lbl.pdf"},{"key":"e_1_2_16_31_1","unstructured":"BESPONSATM US prescribing information (USPI inotuzumab ozogamicin) injection for intravenous use Ref ID: 5341472.FDA Center for Drug Evaluation and Research.2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/761040s003lbl.pdf"},{"key":"e_1_2_16_32_1","unstructured":"BLINCYTO\u00ae US prescribing information (USPI blinatumomab) injection for intravenous use Ref ID: 5680449.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/125557s032lbl.pdf"},{"key":"e_1_2_16_33_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation DANYELZA (naxitamab\u2010gqgk) BLA 761171 Ref ID: 4707829.FDA Center For Drug Evaluation and Research.2020.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/761171Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_34_1","unstructured":"RITUXAN\u00ae US prescribing information (USPI rituximab) injection for intravenous use Ref ID: 4906813.FDA Center for Drug Evaluation and Research.2021.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/103705s5467lbl.pdf"},{"key":"e_1_2_16_35_1","unstructured":"BLA multidisciplinary review and evaluation asparlas (Calaspargase pegol \u2010 mknl) BLA 761102 Ref ID: 4365594.FDA Center For Drug Evaluation and Research.2018.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/761102Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_36_1","unstructured":"VIDAZA US prescribing information (USPI azacitidine) injection for subcutaneous or intravenous use Ref ID: 5767070.FDA Center for Drug Evaluation and Research.2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/050794s036lbl.pdf"},{"key":"e_1_2_16_37_1","unstructured":"VYXEOS\u00ae US prescribing information (USPI daunorubicin and cytarabine) liposome for injection for intravenous use Ref ID: 5734596.FDA Center for Drug Evaluation and Research.2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2026\/209401s018lbl.pdf"},{"key":"e_1_2_16_38_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation MODEYSO (dordaviprone) NDA 219876 Ref ID: 5638121.FDA Center For Drug Evaluation and Research.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2025\/219876Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_39_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation IWILFIN (eflornithine) NDA 215500 Ref ID: 5293087.FDA Center For Drug Evaluation and Research.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/215500Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_40_1","unstructured":"NDA multidisciplinary review and evaluation revumenib NDA 218944 Ref ID: 5478470.FDA Center For Drug Evaluation and Research.Accessed April 3 2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/218944Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_41_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation grafapex (Treosulfan) NDA 214759 Ref ID: 5515086.FDA Center For Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2025\/214759Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_42_1","unstructured":"KOSELUGO\u00ae US prescribing information (USPI selumetinib) capsules for oral use oral granules Ref ID: 5697061.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/213756s006lbl.pdf"},{"key":"e_1_2_16_43_1","unstructured":"XALKORI\u00ae US prescribing information (USPI crizotinib) capsules for oral use oral pellets Ref ID: 5239813.FDA Center for Drug Evaluation and Research.2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/202570s036lbl.pdf"},{"key":"e_1_2_16_44_1","unstructured":"TAFINLAR\u00ae US prescribing information (USPI dabrafenib) capsule for oral use tablets for oral suspension Ref ID: 5770660.FDA Center for Drug Evaluation and Research.2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2026\/202806s40lbl.pdf"},{"key":"e_1_2_16_45_1","unstructured":"NDA multidisciplinary review and evaluation larotrectinib NDA 210861 and 211710 Ref ID: 4354090.FDA Center For Drug Evaluation and Research.2018. Accessed April 3 2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_46_1","unstructured":"TASIGNA\u00ae US prescribing information (USPI nilotinib) capsules for oral use Ref ID: 5325805.FDA Center for Drug Evaluation and Research.2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/022068s041lbl.pdf"},{"key":"e_1_2_16_47_1","unstructured":"NDA\/BLA multidisciplinary review and evaluation GAMIFANT (emapalumab) BLA 761107 Ref ID: 4351404.FDA Center For Drug Evaluation and Research.2018.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/761107Orig1s000MultidisciplineR.pdf"},{"key":"e_1_2_16_48_1","unstructured":"U.S. Food & Drug Administration (FDA).Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans Guidance for Industry.2020. Accessed February 4 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/pediatric\u2010study\u2010plans\u2010content\u2010and\u2010process\u2010submitting\u2010initial\u2010pediatric\u2010study\u2010plans\u2010and\u2010amended"},{"key":"e_1_2_16_49_1","unstructured":"U.S. Food & Drug Administration (FDA).Pediatric Study Plans for Oncology Drugs: Transitional Information Until Full Implementation of FDARA Section 504 Questions and Answers Guidance for Industry.2020. Accessed April 3 2026.https:\/\/fda.report\/media\/134155\/Pediatric+Study+Plans+for+Oncology+Drugs+QA+Draft+Guidance.pdf"},{"key":"e_1_2_16_50_1","unstructured":"U.S. Food & Drug Administration (FDA).Pediatric Drug Development: Regulatory Considerations\u2014Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act Guidance for Industry.2023. Accessed February 4 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/pediatric\u2010drug\u2010development\u2010regulatory\u2010considerations\u2010complying\u2010pediatric\u2010research\u2010equity\u2010act\u2010and"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u2010NB2020\u2010081"},{"key":"e_1_2_16_52_1","unstructured":"U.S. Food & Drug Administration (FDA).Oncology Center of Excellence. Accessed April 3 2026.https:\/\/www.fda.gov\/about\u2010fda\/fda\u2010organization\/oncology\u2010center\u2010excellence"},{"key":"e_1_2_16_53_1","unstructured":"U.S. Congress.Best Pharmaceuticals for Children Act (BPCA) Public Law 107\u2013109 (as amended). Accessed February 4 2026.https:\/\/www.congress.gov\/107\/plaws\/publ109\/PLAW\u2010107publ109.pdf"},{"key":"e_1_2_16_54_1","volume-title":"Regulation (EC) No 1901\/2006 and Regulation (EC) No 1902\/2006 on Medicinal Products for Paediatric Use","author":"European Parliament and Council"},{"key":"e_1_2_16_55_1","unstructured":"Official Journal of the European Union.Guideline on the format and content of applications for agreement or modification of a paediatric investigation plan and requests for waivers or deferrals.2008. Accessed April 3 2026.https:\/\/www.ema.europa.eu\/en\/documents\/other\/communication\u2010commission\u2010guideline\u2010format\u2010and\u2010content\u2010applications\u2010agreement\u2010or\u2010modification\u2010paediatric\u2010investigation\u2010plan\u2010and\u2010requests\u2010waivers\u2010or\u2010deferrals\u2010and\u2010concerning\u2010operation\u2010o_en.pdf"},{"key":"e_1_2_16_56_1","unstructured":"European Medicines Agency (EMA).Policy on the determination of the condition(s) for a paediatric investigation plan\/waiver.2024. Accessed February 4 2026.https:\/\/www.ema.europa.eu\/en\/documents\/other\/policy\u2010determination\u2010conditions\u2010paediatric\u2010investigation\u2010plan\u2010pip\u2010waiver\u2010scope\u2010pip\u2010waiver_en.pdf"},{"key":"e_1_2_16_57_1","unstructured":"European Medicines Agency (EMA).Guidance for Stepwise PIPs (sPIPs).2025. Accessed February 4 2026.https:\/\/www.ema.europa.eu\/en\/documents\/regulatory\u2010procedural\u2010guideline\/guidance\u2010stepwise\u2010pips\u2010spips_en.pdf"},{"key":"e_1_2_16_58_1","unstructured":"U.S. Food & Drug Administration (FDA).Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Guidance for Industry.2023. Accessed February 4 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/formal\u2010meetings\u2010between\u2010fda\u2010and\u2010sponsors\u2010or\u2010applicants\u2010pdufa\u2010products"},{"key":"e_1_2_16_59_1","unstructured":"FDA.Oncology Center of Excellence. Pediatric oncology program overview. Accessed March 16 2026.https:\/\/www.fda.gov\/about\u2010fda\/fda\u2010organization\/oncology\u2010center\u2010excellence"},{"key":"e_1_2_16_60_1","unstructured":"European Medicines Agency (EMA).Reflection paper on the use of extrapolation in the development of medicines for paediatrics.2018. Accessed February 4 2026.https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/adopted\u2010reflection\u2010paper\u2010use\u2010extrapolation\u2010development\u2010medicines\u2010paediatrics\u2010revision\u20101_en.pdf"},{"key":"e_1_2_16_61_1","unstructured":"European Medicines Agency (EMA).Scientific advice and protocol assistance. Accessed February 4 2026.https:\/\/www.ema.europa.eu\/en\/human\u2010regulatory\u2010overview\/research\u2010development\/scientific\u2010advice\u2010protocol\u2010assistance"},{"key":"e_1_2_16_62_1","unstructured":"European Medicines Agency (EMA).Cluster activities. Accessed April 3 2026.https:\/\/www.ema.europa.eu\/en\/partners\u2010networks\/international\u2010activities\/cluster\u2010activities"},{"key":"e_1_2_16_63_1","unstructured":"European Medicines Agency (EMA).Parallel scientific advice and special development aspects or product types. Accessed February 4 2026.https:\/\/www.ema.europa.eu\/en\/human\u2010regulatory\u2010overview\/research\u2010development\/scientific\u2010advice\u2010protocol\u2010assistance\/parallel\u2010scientific\u2010advice\u2010special\u2010development\u2010aspects\u2010or\u2010product\u2010types"},{"key":"e_1_2_16_64_1","unstructured":"National Health Commission of the People's Republic of China.Opinion on reforming and improving the supply assurance mechanism for pediatric medicines (NHC [2026]No. 10). Accessed June 8 2026.https:\/\/www.gov.cn\/zhengce\/zhengceku\/202605\/content_7068031.htm"},{"key":"e_1_2_16_65_1","unstructured":"Pharmaceuticals and Medical Devices Agency (PMDA). Partial revision of \u201cPlanning of the Pediatric Drug Development Program during Development of Drugs for Adults\u201d. Accessed March 26 2026.https:\/\/www.pmda.go.jp\/files\/000268523.pdf"},{"key":"e_1_2_16_66_1","unstructured":"European Medicines Agency (EMA).Concept paper on the development of a reflection paper on proof\u2010of\u2010concept data to support the development of anti\u2010cancer medicinal products in paediatric patients.2026. Accessed March 25 2026.https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/concept\u2010paper\u2010development\u2010reflection\u2010paper\u2010proof\u2010concept\u2010data\u2010support\u2010development\u2010anti\u2010cancer\u2010medicinal\u2010products\u2010paediatric\u2010patients_en.pdf"},{"key":"e_1_2_16_67_1","unstructured":"U.S. Food & Drug Administration (FDA).FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act Guidance for Industry.2021. Accessed March 16 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/fdara\u2010implementation\u2010guidance\u2010pediatric\u2010studies\u2010molecularly\u2010targeted\u2010oncology\u2010drugs\u2010amendments\u2010sec"},{"key":"e_1_2_16_68_1","unstructured":"U.S. Food & Drug Administration (FDA).Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations Guidance for Industry.2023. Accessed March 17 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/pediatric\u2010drug\u2010development\u2010under\u2010pediatric\u2010research\u2010equity\u2010act\u2010and\u2010best\u2010pharmaceuticals\u2010children\u2010act"},{"key":"e_1_2_16_69_1","unstructured":"U.S. Food & Drug Administration (FDA).CDER\/Office of New Drugs Streamlined Nonclinical Studies and Acceptable New Approach Methodologies (NAMs). Accessed March 17 2026.https:\/\/www.fda.gov\/about\u2010fda\/center\u2010drug\u2010evaluation\u2010and\u2010research\u2010cder\/cderoffice\u2010new\u2010drugs\u2010streamlined\u2010nonclinical\u2010studies\u2010and\u2010acceptable\u2010new\u2010approach\u2010methodologies\u2010nams"},{"key":"e_1_2_16_70_1","unstructured":"U.S. Food & Drug Administration (FDA).Severely Debilitating or Life\u2010Threatening Hematologic Disorders: Nonclinical Development of Pharmaceuticals Guidance for Industry.2019. Accessed March 17 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/severely\u2010debilitating\u2010or\u2010life\u2010threatening\u2010hematologic\u2010disorders\u2010nonclinical\u2010development"},{"key":"e_1_2_16_71_1","unstructured":"U.S. Food & Drug Administration (FDA).Monoclonal Antibodies: Streamlined Nonclinical Safety Studies Guidance for Industry.2025. Accessed March 17 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/monoclonal\u2010antibodies\u2010streamlined\u2010nonclinical\u2010safety\u2010studies"},{"key":"e_1_2_16_72_1","unstructured":"U.S. Food & Drug Administration (FDA).S11 Nonclinical Safety Testing In Support of Development of Pediatric Pharmaceuticals Guidance for Industry.2021. Accessed January 23 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/s11\u2010nonclinical\u2010safety\u2010testing\u2010support\u2010development\u2010pediatric\u2010pharmaceuticals"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.70030"},{"key":"e_1_2_16_74_1","unstructured":"U.S. Food & Drug Administration (FDA).Pediatric high\u2010risk cancer preclinical model resource. Accessed April 3 2026.https:\/\/www.fda.gov\/about\u2010fda\/oncology\u2010center\u2010excellence\/pediatric\u2010high\u2010risk\u2010cancer\u2010preclinical\u2010model\u2010resource"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.02.012"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201042745\u20102"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1414311"},{"key":"e_1_2_16_78_1","unstructured":"U.S. Food & Drug Administration (FDA).E11A pediatric extrapolation.2024. Accessed January 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/e11a\u2010pediatric\u2010extrapolation"},{"key":"e_1_2_16_79_1","unstructured":"Friends of Cancer Research.Seamless clinical trial designs in rare cancers: leveraging operational and adaptive strategies to accelerate drug development. Accessed March 25 2026.https:\/\/friendsofcancerresearch.org\/wp\u2010content\/uploads\/Seamless\u2010Clinical\u2010Trial\u2010Designs\u2010in\u2010Rare\u2010Cancers\u2010Leveraging\u2010Operational\u2010and\u2010Adaptive\u2010Strategies\u2010toAccelerate\u2010Drug\u2010Development\u20101.pdf"},{"key":"e_1_2_16_80_1","unstructured":"U.S. Food & Drug Administration (FDA).General Clinical Pharmacology Considerations for Pediatric Studies of Drugs Including Biological Products: Guidance for Industry (Draft).2022. Accessed March 17 2026.https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/general-clinical-pharmacology-considerations-pediatric-studies-drugs-including-biological-products"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010016\u20109499\u20104"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12713"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441\u2010025\u201000864\u20101"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20100491"},{"key":"e_1_2_16_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30023\u20101"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02072"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30671\u20100"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2025.115709"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010025\u201007246\u20107"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.098624"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2504964"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30451\u20104"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(18)30426\u20101"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(18)30153\u20104"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010018\u20104042\u20101"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010023\u201000534\u2010x"},{"key":"e_1_2_16_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30693\u2010X"},{"key":"e_1_2_16_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.70243"},{"key":"e_1_2_16_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(22)00541\u20101"},{"key":"e_1_2_16_100_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2005653"},{"key":"e_1_2_16_101_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.10022"},{"key":"e_1_2_16_102_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvaf149.1746"},{"key":"e_1_2_16_103_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102004\u201010\u20103821"},{"key":"e_1_2_16_104_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007848"},{"key":"e_1_2_16_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185\u2010022\u201003388\u20108"},{"key":"e_1_2_16_106_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.3301"},{"key":"e_1_2_16_107_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.4005"},{"key":"e_1_2_16_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(23)00062\u20105"},{"key":"e_1_2_16_109_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.5763"},{"key":"e_1_2_16_110_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.175.175"},{"key":"e_1_2_16_111_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1542146"},{"key":"e_1_2_16_112_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020004144"},{"key":"e_1_2_16_113_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201099\u2010119618"},{"key":"e_1_2_16_114_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdac143"},{"key":"e_1_2_16_115_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127246"},{"key":"e_1_2_16_116_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201005812\u20103"},{"key":"e_1_2_16_117_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00826"},{"key":"e_1_2_16_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010020\u20100869\u20106"},{"key":"e_1_2_16_119_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1605943"},{"key":"e_1_2_16_120_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201025\u201001447"},{"key":"e_1_2_16_121_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010016\u20103220\u20106"},{"key":"e_1_2_16_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(13)70095\u20100"},{"key":"e_1_2_16_123_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201020\u20104224"},{"key":"e_1_2_16_124_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01000"},{"key":"e_1_2_16_125_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(18)30119\u20100"},{"key":"e_1_2_16_126_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714448"},{"key":"e_1_2_16_127_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20100090"},{"key":"e_1_2_16_128_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911326"},{"key":"e_1_2_16_129_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.15.1138"},{"key":"e_1_2_16_130_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.7712"},{"key":"e_1_2_16_131_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774510382799"},{"key":"e_1_2_16_132_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201016\u20100592"},{"key":"e_1_2_16_133_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543406.2019.1636811"},{"key":"e_1_2_16_134_1","doi-asserted-by":"publisher","DOI":"10.51387\/24\u2010NEJSDS61"},{"key":"e_1_2_16_135_1","unstructured":"U.S. Food & Drug Administration (FDA).Use of Bayesian Methodology in Clinical Trials of Drug and Biological Products Guidance for Industry.2026. Accessed April 4 2026.https:\/\/www.fda.gov\/media\/190505\/download"},{"key":"e_1_2_16_136_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35085"},{"key":"e_1_2_16_137_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2005651"},{"key":"e_1_2_16_138_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.6116"},{"key":"e_1_2_16_139_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13098"},{"key":"e_1_2_16_140_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010020\u20100423\u2010x"},{"key":"e_1_2_16_141_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.64"},{"key":"e_1_2_16_142_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.905"},{"key":"e_1_2_16_143_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.19"},{"key":"e_1_2_16_144_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.70093"},{"key":"e_1_2_16_145_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12702"},{"key":"e_1_2_16_146_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12801"},{"key":"e_1_2_16_147_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2014.38"},{"key":"e_1_2_16_148_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11082158"},{"key":"e_1_2_16_149_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009051"},{"key":"e_1_2_16_150_1","unstructured":"U.S. Food & Drug Administration (FDA).E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population Guidance for Industry.2018. Accessed April 3 2026.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/e11r1\u2010addendum\u2010clinical\u2010investigation\u2010medicinal\u2010products\u2010pediatric\u2010population"},{"key":"e_1_2_16_151_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics3010053"},{"key":"e_1_2_16_152_1","unstructured":"Approval letter REVUFORJ (revumenib) NDA: 218944 Ref ID: 5479801.FDA Center For Drug Evaluation and Research. Accessed April 3 2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/218944Orig1s000Approv.pdf"},{"key":"e_1_2_16_153_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010020\u201004171\u20104"},{"key":"e_1_2_16_154_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1958"},{"issue":"5","key":"e_1_2_16_155_1","first-page":"396","article-title":"Temozolomide stability in extemporaneously compounded oral suspensions","volume":"10","author":"Trissel LABRF","year":"2006","journal-title":"Int J Pharm Compd"},{"key":"e_1_2_16_156_1","doi-asserted-by":"publisher","DOI":"10.1177\/20406207251399466"},{"key":"e_1_2_16_157_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01672"},{"key":"e_1_2_16_158_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2015.12.002"},{"key":"e_1_2_16_159_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26465"},{"key":"e_1_2_16_160_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010026\u201001236\u20109"},{"key":"e_1_2_16_161_1","doi-asserted-by":"publisher","DOI":"10.3390\/children2020244"},{"key":"e_1_2_16_162_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010025\u201003846\u2010y"},{"key":"e_1_2_16_163_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1767"},{"key":"e_1_2_16_164_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010020\u201000463\u2010y"},{"key":"e_1_2_16_165_1","unstructured":"Friends of Cancer Research. Accessed April 7 2026.https:\/\/friendsofcancerresearch.org\/wp\u2010content\/uploads\/Seamless\u2010Clinical\u2010Trial\u2010Designs\u2010in\u2010Rare\u2010Cancers\u2010Leveraging\u2010Operational\u2010and\u2010Adaptive\u2010Strategies\u2010toAccelerate\u2010Drug\u2010Development\u20101.pdf"},{"key":"e_1_2_16_166_1","unstructured":"CABLIVI\u00ae US prescribing information (USPI caplacizumab\u2010yhdp) injection for intravenous or subcutaneous use Ref ID: 5717398.FDA Center for Drug Evaluation and Research.2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/761112s018lbl.pdf?utm_medium=email&utm_source=govdelivery"},{"key":"e_1_2_16_167_1","unstructured":"U.S. Food & Drug Administration (FDA).Using artificial intelligence & machine learning in the development of drug & biological products.Discussion Paper and Request for Feedback. Accessed June 9 2026.https:\/\/www.fda.gov\/media\/167973\/download"},{"key":"e_1_2_16_168_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2668"},{"key":"e_1_2_16_169_1","doi-asserted-by":"publisher","DOI":"10.1200\/CCI.21.00102"},{"key":"e_1_2_16_170_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13061788"},{"key":"e_1_2_16_171_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2026.2636"},{"key":"e_1_2_16_172_1","unstructured":"U.S. Food & Drug Administration (FDA).Digital Health Technologies for Remote Data Acquisition in Clinical Investigations Guidance for Industry Investigators and Other Stakeholders.2023. Accessed April 4 2026.https:\/\/www.fda.gov\/media\/155022\/download"},{"key":"e_1_2_16_173_1","unstructured":"National Cancer Institute (NCI).NCI\u2010COG Pediatric MATCH Precision Medicine Clinical Trial. Accessed April 8 2026.https:\/\/www.cancer.gov\/research\/infrastructure\/clinical\u2010trials\/featured\/pediatric\u2010match"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70242","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70242","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:45:56Z","timestamp":1784954756000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":172,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jcph.70242"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70242","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70242"}}