A Study to Evaluate ICP-022 in Patients With R/R Marginal Zone Lymphoma (MZL)

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

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

Safety, tolerability evaluation, and anti-tumor effects of ICP-022 in Chinese patients with R/R MZL will be evaluated in approximately 110 subjects. Pharmacokinetics of ICP-022 will be evaluated in approximately 20 subjects.

Study Overview

• Status: Completed
• Conditions: MZL
• Intervention / Treatment: Drug: ICP-022

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230002
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230031
      • Anhui Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 102206
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100039
      • Chinese People's Liberation Army General Hospital Fifth Medical Center
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Union Hospital Affiliated to Fujian Medical University
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • The Second Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
    • Guangzhou, Guangdong, China, 510062
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 519041
      • Guangdong Provincial People's Hospital
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • Affiliated Hospital of Guizhou Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • The Fourth Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Affiliated Cancer Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The first affiliated hospital of Zhengzhou university
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial People's Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430022
      • Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Provincial People's Hospital
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 130061
      • First Hospital of Jilin University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Jinan, Shandong, China, 250063
      • Qilu Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Cancer Hospital Affiliated to Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin cancer hospital
    • Tianjin, Tianjin, China, 300020
      • Hematology Hospital, Chinese Academy of Medical Sciences
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • Zhejiang University Medical School affiliated to the first Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women between 18 and 75 years old
• Histologically confirmed marginal zone lymphoma (MZL), and at least one measurable tumor of greater than 1.5 centimeter outside of the spleen
• Subjects with refractory or relapsed MZL who has received at least 1 but no more than 4 prior therapies for MZL
• 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 have indications for treatment (threatened end-organ function, bulky disease >5cm, symptoms, steady progression, wish to treat)

• Subjects 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 ≥ 75 g/L; ANC ≥ 1.0×109/L, Platelet count ≥ 50×109/L, Hemoglobin ≥ 50 g/L; if bone marrow involvement
  2. Total bilirubin ≤ 1.5× ULN; AST or ALT ≤ 2× ULN; Creatinine ≤ 1.5× ULN; Amylase ≤ ULN and Lipase ≤ ULN
  3. International normalized ratio (INR) ≤ 1.5 ULN
• Life expectancy ≥ 3 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 (except for alopecia)

• 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
• Toxicity must be recovered to ≤ Grade 1 from prior anti-cancer therapy
• Disease significantly affecting gastrointestinal function such as dysphagia, chronic diarrhea, intestinal obstruction, or resection of the stomach
• Prior organ or hematopoietic stem cell transplant
• 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 or BCR pathway inhibitor (PI3K or Syk) and BCL-2 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ICP-022	Drug: ICP-022; ICP-022 (tablets, 50 mg) is given orally at the dose of 150 mg/day from day 1 to day 28 of each cycle for up to a total of 6 cycles or until progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The efficacy measured by overall response rate (ORR) in Part II according to the 2014 International Working Group NHL	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I	The safety of ICP-022 measured by the occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I	Up to 3 years
Area under the concentration time curve up to the time "t" (AUC(0-t))	Area under the concentration time curve up to the time "t" (AUC(0-t)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Maximum plasma drug concentrations (Cmax)	Individual plasma concentrations of ICP-022 will be measured and Cmax will be calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Time of maximum plasma drug concentrations (Tmax)	Time of maximum plasma drug concentrations (Tmax) of ICP-022 will be recorded.	up to 4 weeks
Apparent half-life for designated elimination phases (t½)	Apparent half-life for designated elimination phases (t½) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Area under the concentration time curve up to the last data point above LOQ (AUC(last))	Area under the concentration time curve up to the last data point above LOQ (AUC(last)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Progressioin free survival (PFS)	Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.	Up to 3 years
Duration of Response (DR)	Duration of response as defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.	Up to 3 years
Overall survival (OS)	Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.	Up to 3 years

Collaborators and Investigators

• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
• Investigators: Principal Investigator: Jun Zhu, PHD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): December 27, 2023
• Study Completion (Actual): February 6, 2024

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone
• Other Study ID Numbers: ICP-CL-00104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No