Clinical trial NCT06245941: A Clinical Trial of TQ05105 Tablets Combined With TQB3909 Tablets in the Treatment of Myelofibrosis (MF)
Official title: A Phase Ib/II Clinical Trial of TQ05105 Tablets Combined With TQB3909 Tablets in the Treatment of Moderate- and High-risk Myelofibrosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myelofibrosis
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-07
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy and safety of TQ05105 tablets combined with TQB3909 tablets in patients with moderate- and high-risk Myelofibrosis.


Eligibility criteria: Inclusion Criteria:

* Voluntarily participate in the study and signed informed consent with good compliance;
* Age: 18 or above (when signing the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 2; Life expectancy ≥ 24 weeks;
* Patients diagnosed with Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV-MF), or post essential thrombocythemia myelofibrosis (post-ET-MF);
* Those with moderate or high risk myelofibrosis evaluated according to Dynamic International Prognostic Scoring System (DIPSS) prognostic grading criteria, or those with high risk myelofibrosis according to National Comprehensive Cancer Network (NCCN) guidelines prognostic grading criteria;
* Patients with poor efficacy of JAK inhibitors (for monotherapy of TQB3909, phase Ib and phase II cohort 2);
* Patients who had not received JAK inhibitor treatment (for phase Ib and phase II cohort 2)
* Spleen enlargement;
* Peripheral blood primary cells and bone marrow primary cells are ≤10%;
* No growth factor, colony stimulating factor, thrombopoietin or platelet transfusion was received within 2 weeks before the examination, and the blood routine indexes met the requirements within 7 days before the first administration
* The Main organ function is normal;
* Men and women of childbearing age should agree to use contraceptive measures during the study period and within 6 months after the end of the study.

Exclusion Criteria:

* Patients who have previously received allogeneic stem cell transplantation, or received autologous stem cell transplantation within 3 months before the first administration, or recently planned stem cell transplantation;
* Patients who have previously received BCL-2 inhibitor combined with JAK inhibitor therapy;
* Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
* Other malignancies within 3 years prior to first administration or currently present.
* Patients with multiple factors affecting oral or absorption of drugs;
* Major surgical treatment or significant traumatic injury within 4 weeks prior to first administration;
* Presence of congenital bleeding disorder and congenital coagulopathy;
* Patients who had arterial/venous thrombosis events within 6 months before the first administration.
* Have a history of mental drug abuse, or have a mental disorder.
* Active or uncontrolled severe infection;
* Active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection , or active Corona Virus Disease 2019 (COVID-19) infection;
* Patients with grade III or above congestive heart failure, unstable angina pectoris or myocardial infarction, or arrhythmia requiring treatment, or QT interval prolongation within 6 months before the first administration;
* Unsatisfactory blood pressure control despite standard therapy;
* Patients with renal failure requiring hemodialysis or peritoneal dialysis;
* Patients newly diagnosed with pulmonary interstitial fibrosis or drug-related interstitial lung disease within 3 months before the first administration;
* Patients with a history of immunodeficiency disease or organ transplantation;
* Patients with epilepsy requiring treatment;
* Patients with uncontrolled pleural effusion, pericardial effusion or ascites;
* There is a history of attenuated live vaccine inoculation within 4 weeks before the first administration, or attenuated live vaccine inoculation was planned during the study period.
* People with known hypersensitivity to the study drug and excipients;
* Patients diagnosed as active autoimmune diseases within 2 years before the first administration;
* Those who participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first administration
* Any MF treatment drugs, any immunomodulators, or any immunosuppressants were used within 2 weeks prior to the first dose
* According to the judgment of the investigators, some situations seriously endanger the safety of the subjects or affect the subjects to complete the study.

Primary outcomes:
measure: Maximal tolerance dose (MTD)
timeFrame: Up to 2 years.
measure: Recommended phase II dose (RP2D)
timeFrame: Up to 2 years
measure: 35% reduction in spleen volume (SVR35) at week 24
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Optimum effective rate
timeFrame: Up to 120 weeks
measure: Onset time of splenic response
timeFrame: Up to 120 weeks
measure: Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR)
timeFrame: Up to 120 weeks
measure: Percentage change in spleen volume from baseline
timeFrame: Up to 60 weeks
measure: SVR35 at week 60
timeFrame: Up to 60 weeks
measure: Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF-TSS)
timeFrame: Up to 60 weeks
measure: MPN-SAF-TSS decrease
timeFrame: Up to 60 weeks
measure: Progression-free survival (PFS)
timeFrame: Up to 120 weeks
measure: Leukemia free survival (LFS)
timeFrame: Up to 120 weeks
measure: Overall Survival (OS)
timeFrame: Up to 120 weeks
measure: Incidence of adverse events (AEs)
timeFrame: Baseline up to 120 weeks
measure: Severity of adverse events (AEs)
timeFrame: Baseline up to 120 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second People's Hospital of Hefei
state: Anhui
city: Zhengzhou
country: China
facility: Hennan Cancer Hospital
state: Henan
city: Xian
country: China
facility: Xijing Hospital of the Fourth Military Medical University
state: Shaanxi
city: Tianjin
country: China
facility: People's Hospital of Tianjin
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
Study officials:
References: