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3554 A Novel JAK1 Inhibitor SHR0302 for Treatment of Chronic Graft-Verse-Host Disease: A Phase I Clinical Trial

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research, Combination therapy
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Huiying Qiu1*, Qiaomei He1*, Xi Sun1*, Ying Wang2*, Jiahua Niu1*, Jun Yang1*, Chongmei Huang1*, Kun Zhou1*, Yin Tong1*, Yu Cai1*, Baoxia Dong1*, Liping Wan1* and Xianmin Song, phd1

1Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2Clinical Research & Development, Jiangsu Hengrui pharmaceuticals Co., Ltd., Shanghai, China


Chronic graft-versus-host disease (cGVHD) is a frequent and potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Standard steroid first-line treatment could not satisfy therapeutic need due to its limited efficacy. SHR0302 is a highly selective Janus kinase (JAK) 1 inhibitor, which could alleviate symptoms and improve the survival of cGVHD mice in our preclinical study. Herein, we reported updated safety and efficacy results of SHR0302 plus prednisone as first-line treatment for patients with naïve-treatment moderate or severe cGVHD.


This was a Phase I open-label study. Patients who were aged 18-70, and confirmedly diagnosed with first-episode moderate/severe cGVHD requiring systemic immunosuppressive therapy after allo-HSCT were included in the study. cGVHD was defined according to national institutes of health (NIH) criteria. A 3+3 design including five dose levels (1mg/2mg/4mg/6mg/8mg once a day) was implemented to define the optimal dose of SHR0302. Meanwhile, prednisone was concurrently administrated with a dose of 1mg/kg/d and then gradually tapered after two weeks. The primary endpoint was safety, and the secondary endpoints were overall response rate (ORR) at day 28 and week 24. Dose-limiting toxicities (DLTs) were defined as grade 4 hematologic toxicity or grade 3 non-hematologic toxicity associated with SHR0302 which occurred in the first 28 days of study treatment.


From April 2020 to July 2022, 18 patients were enrolled in the trial. Till May 2023, the median follow-up was 17.3 months (range, 1.8-31.7). The median age of the patients was 47 years (range, 31-64). 13 (72.2%) patients had severe cGVHD, and the other 5 had moderate cGVHD. Almost all patients had more than one organ involved, and the most commonly involved organs were skin (66.7%), and mouth (50.0%). In contrast, lung (5.6%) and genital tract (5.6%) involvements were uncommon.

Median duration of SHR0302 treatment was 6.3 months (range, 1.5-23.2). Overall, all (100%) patients experienced adverse events (AEs) related to SHR0302 and/or prednisone, and grade 3 or 4 AEs were observed in 7 (38.89%) patients. The most common SHR0302 treatment-related adverse events (TRAEs) included hypercholesterolemia (61.11%, n=11), hypertriglyceridemia (44.44%, n=8), platelet count decreased (38.89%, n=7), and anemia (16.67%, n=3). There were no serious AEs (SAEs) related with SHR0302, and no patient experienced SHR0302 dose reduction / discontinuation or death due to AEs. Only one patient developed DLT (grade≥3 hypercholesterolemia) in the highest dose-level group who had preexisting hypercholesterolemia. The maximum tolerated dose (MTD) was not reached.

The ORR and complete remission (CR) rates were 94.44% and 27.77% at week 4, and were 82.35% and 64.71% at week 24, respectively. Among 18 evaluable patients, only 1 patient treated at dose level 1 showed no response at week 4. The event-free survival (EFS) at 24 months was 72.20% (95% CI, 51.40%-93.00%). Prednisone was discontinued in 8 (44.4%) patients at 24 weeks and all immunosuppressants, including SHR0302, were stopped in 4 (22.2%) patients with CR before the 24-week assessment.


In summary, SHR0302 in combination with prednisone had a good safety and could achieve a high response for naïve-treatment cGVHD, which suggests that SHR0302 combination might become an optimal choice for naïve-treatment cGVHD.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH