Clinical trial NCT06122831: A Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF)
Official title: A Phase Ib/II Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Intermediate- 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: 2023-11-08
Enrollment: 92
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 TQB3617 Capsules in patients with intermediate- and high-risk Myelofibrosis.


Eligibility criteria: Inclusion Criteria:

* Voluntary and signed informed consent, good compliance.
* Age: 18 or above (when signing the informed consent form); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 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)
* According to the dynamic international prognostic scoring system (DIPSS), patients with intermediate or high risk of bone marrow fibrosis were evaluated.
* Within 7 days before the first administration, the symptom score of myeloproliferative neoplasms should meet certain requirements.
* Patients with poor efficacy of JAK inhibitors (for phase Ib and phase II cohort 2, cohort 3)
* Patients who had not received JAK inhibitor treatment (for phase II cohort 1).
* Spleen enlargement.
* Peripheral blood primary cells and bone marrow primary cells were ≤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 (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study. Serum human chorionic gonadotrophin (HCG) test is not negative within 7 days before the first administration and must be non-lactating patients.

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;
* Previous treatment with BET inhibitors combined with JAK inhibitor;
* Patients who have previously undergone splenectomy, or received splenic radiotherapy within 6 months before the first administration;
* Use of any MF medications, any immunomodulators, any immunosuppressive agents, within 2 weeks prior to first administration (There are separate withdrawal requirements for hydroxyurea, JAK inhibitors, androgen drugs, erythropoietin, long-acting recombinant interferon-α, etc.);
* Other malignancies within 3 years prior to first administration or currently present.
* Patients with multiple factors (such as inability to swallow, postoperative gastrointestinal resection, acute and chronic diarrhea, intestinal obstruction, etc.) 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 and HCV RNA positive, 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 who have received Chinese patent medicines with anti-tumor indications specified in the approved drug package insert of China National Medical Products Administration (NMPA) within 2 weeks before the first administration;
* Patients with uncontrolled pleural effusion, pericardial effusion or ascites;
* There was 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 (except JAK inhibitor-related clinical trials).
* 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)
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: SVR35
timeFrame: Up to 120 weeks
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: Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)
timeFrame: Up to 60 weeks
measure: MPN-SAF TSS change
timeFrame: Up to 120 weeks
measure: Variant allele frequency (VAF)
timeFrame: Up to 48 weeks
measure: The proportion of subjects with gene mutation achieving SVR35
timeFrame: Up to 48 weeks
measure: The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50%
timeFrame: Up to 48 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: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Nanning
country: China
facility: Guangxi Zhuang Autonomous Region People's Hospital
state: Guangxi
city: Cangzhou
country: China
facility: Cangzhou People's Hosipital
state: Hebei
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical College
state: Hebei
city: Tangshan
country: China
facility: North China of Science and Technology University Affiliated Hospital
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Harbin
country: China
facility: The First Hospital of Harbin
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Tongji College Huazhong Unizersity of Science And Technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan University Zhongnan Hospital
state: Hubei
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Wuxi
country: China
facility: The Public Hospital of Wuxi
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Xi'an
country: China
facility: Xi 'An Jiaotong University Second Affiliated Hospital
state: Shaanxi
city: Tai'an
country: China
facility: Tai'an City Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Central Hospital Of Minhang District, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Changzhi
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Tianjin
country: China
facility: People's Hospital of Tianjin City
state: Tianjin
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
Study officials:
References: