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

• ClinicalTrials.gov Identifier: NCT04014205
• Recruitment Status: Recruiting
• First Posted: July 10, 2019
• Last Update Posted: September 23, 2022
• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
• Information provided by (Responsible Party): Beijing InnoCare Pharma Tech Co., Ltd.

Tracking Information

• First Submitted Date: June 18, 2019
• First Posted Date: July 10, 2019
• Last Update Posted Date: September 23, 2022
• Actual Study Start Date: November 18, 2019
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 8, 2021)

• Part 1 Dose Escalation：The maximum tolerated dose (MTD) [ Time Frame: Incidence of dose limiting toxicities (DLTs) up to 28 days ]
  To determine the maximum tolerated dose (MTD)
• Part 2 Dose Expansion：ORR [ Time Frame: Up to 2 years ]
  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.

• Original Primary Outcome Measures (submitted: July 9, 2019): The maximum tolerated dose (MTD) [ Time Frame: Incidence of dose limiting toxicities (DLTs) up to 28 days ]

Current Secondary Outcome Measures (submitted: May 25, 2021)

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

Original Secondary Outcome Measures (submitted: July 9, 2019)

Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability] [ Time Frame: Up to 2 years ]

The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of ICP-022 will be assessed

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: July 9, 2019)

• Objective response rate (ORR) [ Time Frame: Up to 2 years ]
  ORR of ICP-022 will be assessed by the investigator using standard criteria for Non-Hodgkin's lymphoma [2014 Lugano Classification criteria International working group non-hodgkin's lymphoma (IWGNHL) (Cheson et al., 2014) and the International Workshop on Chronic Lymphocytic Leukemia (IWCLL), (Hallek et al., 2008)]
• Elimination half-life (T1/2) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
• Total plasma exposure - Area under the concentration time curve (AUC) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle Day1 pre-dose (-10 minutes) ]
• Time to reach maximum observed plasma concentration (Tmax) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
• Maximum plasma concentration observed (Cmax) [ Time Frame: 28 days/cycle, Cycle 1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle 2 Day1 pre-dose (-10 minutes) ]
• Minimum plasma concentration (Cmin) under steady-state conditions within a dosing interval [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
• clearance (CL) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
• Volume of distribution at steady-state (Vss) [ Time Frame: 28 days/cycle, Cycle 1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]

Descriptive Information

• Brief Title: A Study of Tyrosine Kinase Inhibitor Orelabrutinib (ICP-022) in Patients With r/r B-Cell Malignancies
• Official Title: A Phase I/II，Multicenter, Open-Label, Study of a Novel Bruton's Tyrosine Kinase Inhibitor, Orelabrutinib, in Patients With B-Cell Malignancies
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Part 1：r/r B-cell Malignancies
• Part 2：B-cell Malignancies

Intervention

Drug: Orelabrutinib (ICP-022)

ICP-022 The drug product is a white, round, uncoated tablet

Study Arms

• Experimental: Part 1 Dose Escalation
  Patients with r/r B-cell malignancies including Grades 1-3a FL, MZL, MCL, and CLL/SLL
  Intervention: Drug: Orelabrutinib (ICP-022)
• 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
  Intervention: Drug: Orelabrutinib (ICP-022)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 25, 2021): 81
• Original Estimated Enrollment (submitted: July 9, 2019): 15
• Estimated Study Completion Date: November 30, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Olivia Yang; +1 (609) 524-0684; ClinicalTrialsInfo@innocarepharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04014205
• Other Study ID Numbers: ICP-CL-00107
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Beijing InnoCare Pharma Tech Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Beijing InnoCare Pharma Tech Co., Ltd.
• Verification Date: September 2022