A Study of Tyrosine Kinase Inhibitor ICP-022 in Patients With r/r B-Cell Malignancies
This is a Phase I, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability and pharmacokinetics of a novel BTK inhibitor, ICP-022. During this study, dose escalation will be conducted in patients diagnosed with refractory/relapsed (r/r) B-cell malignancies including only patients with Grades1-3a follicular lymphoma (FL); marginal zone lymphoma (MZL); mantle cell lymphoma (MCL); and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
- Chronic Lymphocytic Leukemia
- Small Lymphocytic Lymphoma
- Follicular Lymphoma
- Mantle Cell Lymphoma
- Marginal Zone Lymphoma
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Signed Informed Consent
- All subjects must meet criteria for requiring therapy at time of enrollment (see treatment indications below)
- Age ≥ 18 years
- Patients with histologically confirmed relapsed or refractory B-cell malignancies, including only patients with Grades 1-3a FL, MZL, MCL, and CLL/SLL
- Patient must had received ≥1 or ≤ 4 prior therapies with documented failure to achieve at least partial response, or disease progression after the most recent systemic treatment
- Patient must have ≥1 measurable lesion site on CT scan (>1.5 cm in longest dimension). Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by MRI instead (Subjects with spleen-only disease are considered as not having measurable disease)
- Electrocorticogram(ECOG) performance status of 0 ~1
- Life expectancy (in the opinion of the investigator) of ≥ 4 months
- Adequate liver function at time of screening: Total bilirubin ≤ 2.0 x Upper Limit of Normal (ULN) (Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible); Aspartate aminotransferase(AST)/ Alanine Aminotransferase(ALT) ≤ 2.5 × ULN
- Coagulation test: at time of screening, international normalized ratio (INR) ≤1.5, and the activated partial thromboplastin time (APTT) ≤ 1.5× ULN
- Adequate hematological function at time of screening: complete blood count tests should be independent of support therapies (i.e., growth factors, or transfusion) and fulfill these criteria: neutrophil count ≥ 1.5 × 109 /L, platelet count ≥ 75 × 109/L, hemoglobin ≥ 80 g/L; if presence of bone marrow infiltration, neutrophil count ≥ 1.0 × 109 /L and platelet count ≥ 50× 109 /L
- Adequate renal function at time of screening: serum creatinine ≤ 1.5 × ULN or creatinine clearance by Cockcroft-Gault formula ≥ 60 mL/min
- Negative test results for Hepatitis B Virus(HBV) ([HBsAg (-)] and non-active HBV or Hepatitis C Virus(HCV) infection:
- Patients who are positive for anti-Hepatitis B Virus core(anti-HBc) antibody must be negative for HBV DNA by Polymerase Chain Reaction (PCR) to be eligible for study participation
- Patients who are positive for HCV antibody must be negative for HCV RNA by PCR to be eligible for study participation.
- Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential and who are considered to be postmenopausal (≥ 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test.
- Patients must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of <1 % per year from screening until (a) 1 month if the patient is a male or (b) 2 months if patient is a female after the last dose of Innocare Pharma-022(ICP-022).
- Pregnant or breast-feeding or intending to become pregnant during the study
- Prior treatment with systemic immunotherapeutic agents, including but not limited to cytokine therapy and anti-CTLA4, anti-Programmed death 1(anti-PD1) and anti- Programmed cell death 1 ligand 1(anti-PDL1) therapeutic antibodies, within 12 weeks or five half-lives of the drug, whichever is shorter, before first dose of ICP-022
- Treatment with any Bruton's tyrosine kinase inhibitor(BTKi), phosphatidylinositol 3 kinase( PI3Ki) or B-cell lymphoma-2(BCL-2) inhibitor
- Patients with known allergies to ICP-022 or its excipients
- Treatment with any chemotherapeutic agent, or treatment with any other investigational therapies including but not limited to anti-cancer agent (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks prior to first dose of ICP-022
- History of allogeneic stem-cell (or other organ) transplantation
- Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug
- Concurrent use of warfarin or other vitamin K antagonists or anticoagulation therapies
- Concurrent use of a strong Cytochrome P450 3A (CYP3A) inhibitor. Subjects who have received a strong CYP3A inhibitor prior to entering the study must have discontinued therapy for at least 5 half-lives of the prohibited medication.
- Active uncontrolled infections
- Recent infection requiring IV anti-infective treatment that was completed ≤14 days before the first dose of study drug
- Known infection with HIV, seropositive status
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) ≤ Grade 1, or to the levels dictated in the eligibility criteria with the exception of alopecia.
- Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
- Medically apparent central nervous system(CNS) lymphoma or leptomeningeal disease
- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator, are allowed
17. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, abusing of alcohol or illegal drugs including non-prescribed marijuana within last 6 months from screening.
18. Major surgery or significant traumatic injury < 28 days prior to the first dose of ICP-022 (excluding biopsies) or anticipation of the need for major surgery during study treatment
19. Patients with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the investigator to be of low likelihood for recurrence)
20. Significant cardiovascular disease such as New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
21. Significant active pulmonary disease (e.g., bronchospasm and/or obstructive pulmonary disease)
22. Administration of a live, attenuated vaccine within 28 days before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
23. Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment < 20 mg/day prednisone or equivalent within 7 days prior to first dose of ICP-022
• Inhaled and topical steroids are permitted
24. Unable to swallow tablets or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
- Phase 1
- Study Type
- Intervention Model
- Sequential Assignment
- Primary Purpose
- None (Open Label)
ICP-022 (Lower Dose)
|100 mg, Once a day (QD)||
ICP-022 (Higher Dose)
|150 mg, QD||
- Beijing InnoCare Pharma Tech Co., Ltd.
Study ContactOlivia Yang