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It is shown to have a higher response rate, higher mid\u2010to\u2010long term overall survival, and lower toxicity than standard treatments. However, due to a lack of dose\u2010limiting toxicity (DLT) and unclear dose\u2010effect relationship, traditional phase I designs of clinical trials cannot lead to accurate selections of the optimal dose (OD). Beside clinical outcomes, the CAR\u2010T cell expansion from serial blood samples is measured at various time points. We propose a novel early phase dose\u2010finding design for CAR\u2010T cells, using both toxicity and activity endpoints to locate the OD. The number of CAR\u2010T cells measured in the peripheral blood is used to indicate activity, which is more sensitive than the short\u2010term clinical responses traditionally used. A Bi\u2010Exponential model is used for the repeated measures of the number of cells for each patient, and is estimated under a Bayesian framework. The model is motivated by biological concerns and is flexible enough to accommodate different shapes of the cell\u2010expansion curve. Three criteria for activity are considered: (1) the number of cells at specific time points, (2) the duration before all cells are eliminated, (3) the area under the cell\u2010expansion curve. Simulation studies show that the OD can be selected with high accuracy even under small sample sizes.<\/jats:p>","DOI":"10.1002\/pst.70102","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:19:03Z","timestamp":1781788743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Phase Dose\u2010Finding Designs for\n                    <scp>CAR<\/scp>\n                    \u2010T Cell Therapies"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-5901","authenticated-orcid":false,"given":"Weishi","family":"Chen","sequence":"first","affiliation":[{"name":"MRC Biostatistics Unit University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Mozgunov","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Mullaert","sequence":"additional","affiliation":[{"name":"Clinical Research Division Institut Curie  Paris France"},{"name":"University of Versaille St Quentin\/Paris Saclay  Paris France"},{"name":"STAMPM, INSERM U1331  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Paoletti","sequence":"additional","affiliation":[{"name":"Clinical Research Division Institut Curie  Paris France"},{"name":"University of Versaille St Quentin\/Paris Saclay  Paris France"},{"name":"STAMPM, INSERM U1331  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1706169"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6711"},{"key":"e_1_2_10_4_1","volume-title":"Expansion Cohorts: Use in First\u2010in\u2010Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics\u2014Guidance for Industry","author":"US Food and Drug Administration","year":"2020"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005678"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531693"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210859"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.10.020"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_397912"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0290-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006\u2010341X.2001.01018.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2004.00218.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1864"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00257"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-0420.2005.00314.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.1818"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8889"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10543406.2024.2364716"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2022.100901"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12851"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/3.1.51"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxaa054"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxy045"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03326-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14225576"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12388"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531628"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-51"},{"key":"e_1_2_10_29_1","unstructured":"Y. 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