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

Overview

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.

Interventions

• Drug TQ05105 Tablets
  TQ05105 Tablets is a Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) Inhibitor.
• Drug TQB3617 Capsules
  TQB3617 Capsules is a Bromodomain and Extra-Terminal (BET) Inhibitor

Primary outcome measures

• Maximal tolerance dose (MTD) [Time frame: Up to 2 years.]
• Recommended phase II dose (RP2D) [Time frame: Up to 2 years]
• ≥35% reduction in spleen volume (SVR35) [Time frame: Up to 24 weeks]

Secondary outcome measures (12)

• SVR35 [Time frame: Up to 120 weeks]
• Optimum effective rate [Time frame: Up to 120 weeks]
• Onset time of splenic response [Time frame: Up to 120 weeks]
• Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR) [Time frame: Up to 120 weeks]
• Myeloproliferative neoplasm - Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS) [Time frame: Up to 60 weeks]
• MPN-SAF TSS change [Time frame: Up to 120 weeks]
• Variant allele frequency (VAF) [Time frame: Up to 48 weeks]
• The proportion of subjects with gene mutation achieving SVR35 [Time frame: Up to 48 weeks]
• The proportion of subjects with gene mutation whose MPN-SAF TSS scale decreased by ≥ 50% [Time frame: Up to 48 weeks.]
• Progression-free survival (PFS) [Time frame: Up to 120 weeks]
• Leukemia free survival (LFS) [Time frame: Up to 120 weeks]
• Overall Survival (OS) [Time frame: Up to 120 weeks]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 22 centers

• Guangdong Provincial People's Hospital — Guangzhou
• Guangxi Zhuang Autonomous Region People's Hospital — Nanning
• Cangzhou People's Hosipital — Cangzhou
• Affiliated Hospital of Chengde Medical College — Chengde
• North China of Science and Technology University Affiliated Hospital — Tangshan
• Xingtai People's Hospital — Xingtai
• The First Hospital of Harbin — Harbin
• Henan Cancer Hospital — Zhengzhou
• … and 14 more centers

Identifiers

NCT: NCT06122831 · TQ05105-TQB3617-Ib/II-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗