Clinical trial NCT06186804: A Phase II Study Evaluating the Efficacy and Safety of ABSK021 (Pimicotinib)) in the Treatment of cGvHD Chronic Graft Versus Host Disease (cGvHD)
Official title: A Multicenter, Single-arm, Open-label, Phase II Clinical Study. This Study Consisting of Part A and Part B to Evaluate the Efficacy and Safety of ABSK021 (Pimicotinib) in Patients With Chronic Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: cGvHD
Lead sponsor: Abbisko Therapeutics Co, Ltd
Sponsor class: INDUSTRY
First posted: 2024-01-02
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients will be instructed to take a specified dose of ABSK021 at the same time each day. In Cycle 1, the patient should take one dose every morning after waking up; After the 15th day of the 1st cycle, the specified dose may be taken in the morning or evening, but should be taken at the same time every day.
Primary purpose: TREATMENT

Brief summary: This is a multicenter, single arm, open label phase II clinical study in China. This study will evaluate the efficacy and safety of ABSK021 (Pimicotinib) in the treatment of patients with cGvHD who failed first-line therapy.

Detailed description: This is a phase II, open-label study to evaluate safety, tolerability, pharmacokinetics (PK), and clinical benefit of ABSK021 in patients with hormone refractory or relapsed cGvHD. This study consisted of Part A and Part B, all cGvHD patients in this study will receive continuous oral treatment with ABSK021 once a day (QD) in a 28-day cycle, complete the core treatment period and extended treatment period, and receive regular follow-up until the termination of treatment is determined.

Eligibility criteria: Inclusion Criteria:

1. Sign the informed consent and agree to comply with the requirements and restrictions set out in the informed consent.
2. At the time of signing the informed consent., the patient must be at least 18 years old, regardless of gender ；
3. Allogeneic hematopoietic stem cell transplantation from any donor source using bone marrow, peripheral blood stem cells, or cord blood.
4. Patients who have received at least 1 line of systemic therapy
5. If the patient is being treated with glucocorticoids or calcineurin inhibitor(CNI), the patient should have received a stable dose of the above treatment for not less than 2 weeks prior to the first use of ABSK021.
6. ECOG (Eastern Cooperative Oncology Group Performance Status) physical strength score 0-2;7. The patient had sufficient organ and bone marrow function within 14 days prior to the first use of ABSK021.

8. For patients with Part A only: antifungal drugs that are currently being used in combination with CYP3A4 potent inhibitors should have been continuously used in accordance with regulations for no less than one week before the first use of ABSK021

Exclusion Criteria:

1. In previous treatment, he received highly selective colony stimulating factor 1 receptor (CSF-1R) targeted therapy, including small molecule or large molecule drugs;
2. A known history of allergy to components of the investigational drug composition ;
3. Patients continued to use CYP3A4 in combination with antifungal agents or in the two weeks prior to the initial administration of ABSK021 Strong inducer;
4. The patient has received more than 5 lines of systemic therapy for cGvHD;
5. The patient presented with aGvHD symptoms without cGvHD symptoms ;
6. Any evidence of potential tumor or recurrence of post-transplant lymphoproliferative disease at the screening stage .
7. There are factors that have been determined by the investigators to have a significant influence on oral drug absorption
8. Present with cholestatic disease, or unresolved hepatic sinus obstruction syndrome/venous obstructive disease;
9. active infection.
10. During the screening period, the investigators judged that the patients had insufficient pulmonary function reserve, with FEV1≤ 39% or pulmonary function classification score of 3;
11. Prior treatment (adverse events did not return to ≤ Grade 2 (CTCAE v5.0);
12. Pregnant or lactating women;
13. Patients who are unable to or disagree with contraception.

Primary outcomes:
measure: Dose limited toxicity (DLT) at each dose can assess the incidence of DLT in patients during the observation period of DLT (Part A only)
timeFrame: Starting from the first medication, observe for 31 days
measure: Overall response rate after 6 cycles of treatment
timeFrame: 6 months
Secondary outcomes:
measure: Adverse Events
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of the Army Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Peoplep's Hospital
state: Guangdong
city: Zhujiang
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College,Huazhong University of Science and Technology
state: Hubei
city: Hangzhou
country: China
facility: The Fir St Affiliated Hospital,Zhejiang Univer Sity School of Medicine
state: Jiangsu
city: Suzhou
country: China
facility: The First affiliated hospital of SuZhou University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Hematology Hospital of Chinese Academy of Medical Sciences
state: Tianjin
city: Xinjiang
country: China
facility: The First Teaching Hospital of Xinjiang Medical University
state: Xinjiang
Study officials:
References: