A Study to Evaluate ICP-022 in Patients With R/R Mantle Cell Lymphoma (MCL)

A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of ICP-022 in Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL)

The phase I/II clinical study is to investigate the safety, tolerability and pharmacokinetics/ pharmacodynamics of ICP-022.

Part I: PK/PD and safety evaluation -Two regimens of ICP-022 (High dose QD and low dose BID) were designed for assessment of safety, as well as PK/PD profiles. The recommended dose of phase II clinical study will be determined according to the Part I results.

Part II: Dose expansion -Anti-tumor effects of ICP-022 in Chinese patients with R/R MCL will be evaluated in approximately 80 subjects. The recommended Phase 2 dose will be used in the Part II.

Inclusion Criteria:

• Men and women between 18 and 75 years old

• Histologically confirmed mantle cell lymphoma (MCL), with either t(11;14) by cytogenetics and/or cyclin D1 overexpression by immunohistochemistry (IHC)

• Subjects with refractory or relapsed mantle cell lymphoma who has received at least 1 but no more than 4 prior therapies for MCL

• At least one measurable tumor of greater than 1.5 centimeter in long axis by contrast-enhanced CT/MRI

• ECOG performance status of 0-2

• Documented failure to achieve at least partial response (PR) or documented disease progression after response to, the most recent treatment regimen.

• Subjects who meet the following laboratory parameters:

  1. Absolute neutrophil count (ANC) ≥ 1.5×109/L Platelet count ≥ 75×109/L, independent of growth factor support within 7 days of the first dose with study drug, Hemoglobin ≥ 80 g/L; ANC ≥ 1.0×109/L, Platelet count ≥ 50×109/L if bone marrow involvement
  2. Total bilirubin ≤ 2× ULN; AST or ALT ≤ 2.5 ULN; Creatinine clearance ≥ 30ml/min; Amylase ≤ ULN and Lipase ≤ ULN
  3. International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN

• Life expectancy ≥ 4 months

• Able to provide signed written informed consent

Exclusion Criteria:

• History of other active malignancies within 5 years of study entry, unless cured without evidence of relapse or metastasis

• Current or history of lymphoma involved central nervous system

• Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, radiation therapy, or antibody based therapies or anti-cancer TCM within 4 weeks of the start of study drug.

• Non-hematological toxicity must recover to ≤ Grade 1 from prior anti-cancer therapy

• Current clinically significant cardiovascular disease including:

  • Any class 3 or 4 cardiac disease such as arrhythmia, congestive heart failure or myocardial infarction defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) < 50%
  • Primary cardiomyopathy
  • Clinical significant QTc prolong history or QTc>470ms (female) QTc>450ms (male)
  • Uncontrolled hypertension

• Known active bleeding within 2 months of screening or currently taking anticoagulant/antiplatelet drugs

• Urine protein ≥ 2+ and quantitation ≥ 2g/24hours

• History of deep vein thrombosis or pulmonary embolism

• Disease significantly affecting gastrointestinal function such as dysphagia, chronic diarrhea, intestinal obstruction, or resection of the stomach

• Allogeneic stem cell transplant within 6 months prior to first dose of study drug or related active infection

• Major surgery within 6 weeks of screening, except for diagnostic test or vascular access setup

• Known active infection with HBV, HCV or HIV or any uncontrolled active systemic infection

• Any history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe lung function impairment

• Prior exposure to a BTK inhibitor，BCR pathway ingibitor(such as PI3K, SYK) or BCL-2 kinase inhibitor

• Suitable and ready for allogeneic stem cell transplant

• Inability to comply with study procedures

• Drug abuser or alcoholics

• Lactating or pregnant women, or women who will not use contraception during the study and for 180 days after the last dose of study drug if sexually active and able to bear children

• Requires treatment with moderate or strong cytochrome P450 family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.