{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:10:22Z","timestamp":1789996222279,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Early clinical development of anticancer drugs traditionally focused on exploring candidate treatments in patients. For instance, due to their cytotoxic action, administration of chemotherapies to healthy volunteers (HVs) for evaluation of their pharmacokinetic profiles was not considered feasible nor ethical from a safety and tolerability perspective. With the introduction of more targeted anticancer agents, such as the tyrosine kinase inhibitors (TKIs), enrolment of HVs in clinical pharmacology trials has become an advantageous alternative to early, non\u2010therapeutic testing in cancer patients. Futibatinib (Lytgobi) is a TKI acting upon the fibroblast growth factor receptor (FGFR) 1\u20134 and is approved for the treatment of patients with locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangement. During its clinical development, a series of studies were conducted enrolling HVs, for example, to evaluate pharmacokinetic properties (ADME), drug\u2013drug interaction (DDI) potential and QT liability. In this review article, we will discuss when and why enrolment of HVs can be considered for small molecule anticancer drug trials and touch upon the risks and limitations as well as the advantages of administering this type of drugs to HVs. The case of futibatinib provides an illustrative example of the opportunities and challenges for exploring an anticancer small molecule in HVs.<\/jats:p>","DOI":"10.1111\/cts.70711","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:21:41Z","timestamp":1788420101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging Healthy Volunteers for Anticancer Drug Clinical Pharmacology Studies: A Review Article Featuring Futibatinib as an Example"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6296-2123","authenticated-orcid":false,"given":"Aernout D.","family":"van Haarst","sequence":"first","affiliation":[{"name":"Celerion Inc.  Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-942X","authenticated-orcid":false,"given":"Sabina","family":"Paglialunga","sequence":"additional","affiliation":[{"name":"Celerion Inc.  Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziv","family":"Machnes","sequence":"additional","affiliation":[{"name":"Celerion Inc.  Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Yamamiya","sequence":"additional","affiliation":[{"name":"Taiho Oncology Inc.  Pleasanton California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9190-4920","authenticated-orcid":false,"given":"Nanae","family":"Hangai","sequence":"additional","affiliation":[{"name":"Taiho Oncology Inc.  Pleasanton California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram","family":"Oganesian","sequence":"additional","affiliation":[{"name":"Taiho Oncology Inc.  Pleasanton California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111659"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010020\u201000977\u20100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010023\u201004729\u20104"},{"key":"e_1_2_10_5_1","unstructured":"U.S. Food and Drug Administration \u201cImatinib\u2015Clinical Pharmacology and Biopharmaceutics Review(s) NDA 21\u2010335 \u201d accessed June 11 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2001\/21\u2010335_Gleevec_biopharmr_P1.pdf."},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12703"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15092"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441\u2010021\u201000330\u20108"},{"key":"e_1_2_10_9_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Grants Accelerated Approval to Futibatinib for Cholangiocarcinoma \u201d(2022) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010accelerated\u2010approval\u2010futibatinib\u2010cholangiocarcinoma."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201023\u20101042"},{"key":"e_1_2_10_11_1","unstructured":"U.S. Food and Drug Administration \u201cFutibatinib\u2014Multi\u2010Disciplinary Review NDA 214801 \u201d accessed June 11 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2022\/214801Orig1s000MultidisciplineR.pdf."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1259"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1196"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70012"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1271"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1195"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13585"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70094"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70060"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.242909"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1584"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.70040"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1926"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.954806"},{"key":"e_1_2_10_25_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use \u201cGuidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals M3(R2) \u201d (2009) https:\/\/database.ich.org\/sites\/default\/files\/M3_R2__Guideline.pdf."},{"key":"e_1_2_10_26_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use \u201cNonclinical Evaluation for Anticancer Pharmaceuticals S9 \u201d (2009) https:\/\/database.ich.org\/sites\/default\/files\/S9_Guideline.pdf."},{"key":"e_1_2_10_27_1","unstructured":"U.S. Food and Drug Administration \u201cOverview and Difference in Nonclinical Safety Assessments for Small Molecules and Biologic Drug Development \u201d accessed June 11 2025 https:\/\/www.youtube.com\/watch?v=ixAvJhURqmo."},{"key":"e_1_2_10_28_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use \u201cGuidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use S2(R1) \u201d (2011) https:\/\/database.ich.org\/sites\/default\/files\/S2_R1_Guideline.pdf."},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.5"},{"key":"e_1_2_10_30_1","unstructured":"U.S. Food and Drug Administration \u201cEstimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers \u201d (2005) https:\/\/www.fda.gov\/media\/72309\/download."},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1144056"},{"key":"e_1_2_10_32_1","unstructured":"Food and Drug Administration \u201cOptimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases: Guidance for Industry \u201d (2024) https:\/\/www.fda.gov\/media\/164555\/download."},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00371"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.06.018"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101204"},{"key":"e_1_2_10_36_1","unstructured":"\u201cLYTGOBI (Futibatinib) Tablets for Oral Use \u201d (2022) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/214801s000lbl.pdf."},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001469\u20106"},{"key":"e_1_2_10_38_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use \u201cDrug Interaction Studies M12 \u201d (2024) https:\/\/database.ich.org\/sites\/default\/files\/ICH_M12_Step4_Guideline_2024_0521_0.pdf."},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3284"},{"key":"e_1_2_10_40_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use \u201cClinical and Nonclinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential\u2014Questions and Answers E14\/S&B Q&As \u201d (2022) https:\/\/database.ich.org\/sites\/default\/files\/E14\u2010S7B_QAs_Step4_2022_0221.pdf."},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268\u2010023\u201000440\u20108"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.896"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12779"},{"key":"e_1_2_10_44_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use \u201cThe Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs E14 \u201d (2005) https:\/\/database.ich.org\/sites\/default\/files\/E14_Guideline.pdf."},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206834"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15486"},{"key":"e_1_2_10_47_1","unstructured":"U.S. Food and Drug Administration \u201cErdafitinib\u2014Multi\u2010Disciplicary Review NDA 212018 \u201d accessed June 11 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2019\/212018Orig1s000MultidisciplineR.pdf."},{"key":"e_1_2_10_48_1","unstructured":"U.S. Food and Drug Administration \u201cPemigatinib\u2015Multi\u2010Discipline Review NDA 213736 \u201d accessed June 11 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/213736Orig1s000MultidisciplineR.pdf."},{"key":"e_1_2_10_49_1","unstructured":"U.S. Food & Drug Administration \u201cWITHDRAWN: FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma \u201d (2024) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/withdrawn\u2010fda\u2010grants\u2010accelerated\u2010approval\u2010infigratinib\u2010metastatic\u2010cholangiocarcinoma."},{"key":"e_1_2_10_50_1","unstructured":"U.S. Food and Drug Administration \u201cInfigratinib\u2015Multi\u2010Disciplinary Review NDA 214622 \u201d accessed June 11 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2021\/214622Orig1s000MultidisciplineR.pdf."},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600448"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184689"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201004\u20101371"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1153"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70711","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70711","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70711","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:45:28Z","timestamp":1789994728000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/cts.70711"],"URL":"https:\/\/doi.org\/10.1111\/cts.70711","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70711"}}