Upadacitinib for Immune Checkpoint Inhibitor–Related Dermatitis: A Nonrandomized Clinical Trial
Mené en Chine sur 33 patients atteints d'un cancer traité par inhibiteur de point de contrôle immunitaire, cet essai de phase II non randomisé évalue la toxicité et l'efficacité de l'upadacitib pour soulager une dermatite induite par les traitements
The conventional primary treatment for severe immune checkpoint inhibitor (ICI)–related dermatitis involves high-dose systemic corticosteroids.1 Corticosteroids usually pose significant risks, such as severe infection and gastrointestinal bleeding. Additionally, they attenuate the antitumor efficacy of ICIs.2 Upadacitinib, a selective Janus kinase (JAK) 1 inhibitor, suppresses JAK1 in the JAK-STAT pathway. It is indicated for autoimmune and atopic dermatitis.3 Herein, the study investigators designed a phase 2 clinical trial to evaluate the resolution rate of patients with various solid tumors who have developed severe (grades 3-4) ICI-related dermatitis.
Methods: This single-center, open-label, single-group phase 2 nonrandomized clinical trial was conducted at Quzhou People’s Hospital in Zhejiang, China, with approval from the institutional review board and an independent ethics committee (NCT06715982). All participants provided written informed consent. The study was designed as a Simon 2-stage clinical trial. All analyses were conducted using R version 4.2.0 (R Foundation). The protocol and statistical analysis plan are provided in Supplements 1 and 2, respectively.
Patients diagnosed with grades 3 to 4 ICI-related dermatitis received oral upadacitinib (15 mg/d) for 28 days, without taking concomitant glucocorticoids, immunosuppressants, or antihistamines. Patients whose dermatitis was relieved (defined as a reduction to grade ≤1) were permitted to resume their original antitumor therapy.
The primary end points were upadacitinib safety and ICI-related dermatitis resolution. Resolution was defined as grade 1 or less rashes by day 28. Grade 0 indicated complete resolution, while grade 1 demonstrated partial resolution. Adverse events (AEs) were recorded. Secondary end points included the percentage of patients continuing ICIs at day 28 and the change in pruritus severity assessed by the Peak Pruritus Numerical Rating Scale. The 95% CIs were calculated using the Jennison-Turnbull method and a 2-sided
α level was set at .05.
Results
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From February to July 2025, 33 of 50 screened patients were enrolled. During the first stage (February-April 2025), the predefined criterion for trial continuation was met, with rash resolution observed in all 14 initial participants. This prompted subsequent enrollment of 19 additional patients in the second stage (April-August 2025). All patients were treatment-naive, with no prior exposure to corticosteroids and other immunosuppressants
JAMA Oncology , résumé, 2026