A Study of Tyrosine Kinase Inhibitor Orelabrutinib (ICP-022) in Patients With r/r B-Cell Malignancies

A Phase I/II，Multicenter, Open-Label, Study of a Novel Bruton's Tyrosine Kinase Inhibitor, Orelabrutinib, in Patients With B-Cell Malignancies

This is a Phase I/II, multicenter, open-label study to evaluate the safety, efficacy, tolerability, and pharmacokinetics of a novel BTK inhibitor, Orelabrutinib (ICP-022) in Patients with B-cell malignancies. The study contains two parts, Part 1 (dose escalation) and Part 2 (dose expansion).

Study Overview

• Status: Active, not recruiting
• Conditions: Part 1：r/r B-cell Malignancies; Part 2：B-cell Malignancies
• Intervention / Treatment: Drug: Orelabrutinib (ICP-022)

• Study Type: Interventional
• Enrollment (Anticipated): 81
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Olivia Yang; Phone Number: +1 (609) 524-0684; Email: ClinicalTrialsInfo@innocarepharma.com

Study Locations

• Israel
  • Be'er Sheva, Israel
    • Soroka Medical Center
  • Haifa, Israel
    • Carmel Medical Center
• Poland
  • Gdansk, Poland
    • Uniwersyteckie Centrum Kliniczne
• Ukraine
  • Cherkasy, Ukraine
    • Cherkassy Regional Oncology Center
  • Khmelnytskyi, Ukraine
    • Khmelnytskyi Regional Hospital
  • Kropyvnytskyi, Ukraine
    • St. Luke's Hospital - Medical and Diagnostic Center
  • Kyiv, Ukraine
    • National Cancer Institute
  • Lviv, Ukraine
    • Institute of blood pathology and transfusion medicine
  • Uzhgorod, Ukraine
    • Transcarpathian Regional Clinical Hospital named after Andrii Novak
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054-4502
      • Mayo Clinic-Mayo Clinic Hospital-Phoenix
  • California
    • Anaheim, California, United States, 92801-1824
      • Pacific Cancer Medical Center
    • Los Angeles, California, United States, 90017
      • Los Angeles Cancer Network - Good Samaritan Hospital Location
    • Rancho Mirage, California, United States, 92270
      • Desert Hematology Oncology Medical Group, Inc.
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope & Innovation
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists (FCS) South
    • Weeki Wachee, Florida, United States, 34607
      • Asclepes Research Centers - Weeki Wachee
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Northwest Neurology - Rolling Meadows Office
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research Inc.
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine - Tulane Cancer Center Comprehensive Clinic TCCCC
  • Maryland
    • Annapolis, Maryland, United States, 21401-3093
      • Anne Arundel Medical Center (AAMC) Oncology and Hematology
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510-2496
      • Southeast Nebraska Cancer Center
  • New Jersey
    • Florham Park, New Jersey, United States, 07932-0001
      • Summit Medical Group
  • New York
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Research Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh - Hillman Cancer Center
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Cancer Center
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404-1130
      • Tennessee Oncology - Chattanooga Oncology & Hematology Associates
    • Knoxville, Tennessee, United States, 37909-1327
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37203-1625
      • Sarah Cannon Research Institute - Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Spokane, Washington, United States, 99201
      • Medical Oncology Associates PS (dba Summit Cancer Centers)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed Informed Consent.
2. Age ≥ 18 years.

3. Part 1: Patients with histologically confirmed relapsed or refractory B-cell malignancies, including Grades 1-3a FL, MZL, MCL, and CLL/SLL.

   Part 2: Patients with histologically confirmed B-cell malignancies including r/r FL, r/r MZL and CLL/SLL with/without prior treatment.

4. Life expectancy (in the opinion of the investigator) of ≥ 4 months.
5. ECOG performance status of 0 ~1.
6. Must have adequate organ function.
7. Negative test results for HBV ([HBsAg (-)] and non-active HBV or HCV infection

Exclusion Criteria:

1. Pregnant or breast-feeding or intending to become pregnant during the study.
2. Prior treatment with systemic immunotherapeutic agents.
3. Known allergies to Orelabrutinib (ICP-022) or its excipients or infection with HIV.
4. Treatment with any chemotherapeutic agent, or any other investigational therapies within 4 weeks prior to first dose of the study drug.
5. History of allogeneic stem-cell (or other organ) transplantation or confirmed progressive PML.
6. Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug.
7. Concurrent use of warfarin or other vitamin K antagonists or anticoagulation therapies or strong CYP3A inhibitor.
8. Active uncontrolled infections.
9. Recent infection requiring IV anti-infective treatment that was completed ≤ 14 days before the first dose of study drug.
10. Unresolved toxicities from prior anti-cancer therapy.
11. Medically apparent CNS lymphoma or leptomeningeal disease.
12. Current or previous history of CNS disease.
13. Major surgery or significant traumatic injury < 28 days prior to the first dose of the study drug.
14. Patients with another invasive malignancy in the last 2 years.
15. Significant cardiovascular disease or active pulmonary disease.
16. Received systemic immunosuppressive medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation; Patients with r/r B-cell malignancies including Grades 1-3a FL, MZL, MCL, and CLL/SLL	Drug: Orelabrutinib (ICP-022); ICP-022 The drug product is a white, round, uncoated tablet
Experimental: Part 2 Dose Expansion; Arm 1: Patients with r/r MCL Arm 2: Patients with other types of B-cell malignancies, including: CLL/SLL with/without prior treatment; r/r FL; r/r MZL	Drug: Orelabrutinib (ICP-022); ICP-022 The drug product is a white, round, uncoated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Dose Escalation：The maximum tolerated dose (MTD)	To determine the maximum tolerated dose (MTD)	Incidence of dose limiting toxicities (DLTs) up to 28 days
Part 2 Dose Expansion：ORR	To assess anti-tumor activity of Orelabrutinib (ICP-022) in Patients with B-cell malignancies including r/r MCL, r/r FL, r/r MZL and CLL/SLL with/without prior treatment.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Dose Escalation：Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]	The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of ICP-022 will be assessed	Up to 2 years
Part 1 Dose Escalation：ORR	Objective response rate	Up to 2 years
Part 1 Dose Escalation：T1/2	Elimination half-life	Up to 2 years
Part 2 Dose Expansion：Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]	The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of ICP-022 will be assessed	Up to 2 years
Part 2 Dose Expansion：DOR	Duration of response	Up to 2 years

Collaborators and Investigators

• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): January 30, 2025

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ICP-CL-00107

Drug and device information, study documents

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