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

Study Overview
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Brief Summary
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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).

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

Conditions
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Part 2：B-cell Malignancies, Part 1：r/r B-cell Malignancies

Intervention / Treatment
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* Drug: Orelabrutinib (ICP-022)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent. Age ≥ 18 years. 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. Life expectancy (in the opinion of the investigator) of ≥ 4 months. ECOG performance status of 0  1. Must have adequate organ function. Negative test results for HBV ([HBsAg (-)] and non-active HBV or HCV infection Exclusion Criteria: Pregnant or breast-feeding or intending to become pregnant during the study. Prior treatment with systemic immunotherapeutic agents. Known allergies to Orelabrutinib (ICP-022) or its excipients or infection with HIV. Treatment with any chemotherapeutic agent, or any other investigational therapies within 4 weeks prior to first dose of the study drug. History of allogeneic stem-cell (or other organ) transplantation or confirmed progressive PML. 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 or strong CYP3A inhibitor. Active uncontrolled infections. Recent infection requiring IV anti-infective treatment that was completed ≤ 14 days before the first dose of study drug. Unresolved toxicities from prior anti-cancer therapy. Medically apparent CNS lymphoma or leptomeningeal disease. Current or previous history of CNS disease. Major surgery or significant traumatic injury < 28 days prior to the first dose of the study drug. Patients with another invasive malignancy in the last 2 years. Significant cardiovascular disease or active pulmonary disease. Received systemic immunosuppressive medications.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Dose Escalation<br>Patients with r/r B-cell malignancies including Grades 1-3a FL, MZL, MCL, and CLL/SLL | Drug: Orelabrutinib (ICP-022)<br>* ICP-022 The drug product is a white, round, uncoated tablet<br>|
| Experimental: Part 2 Dose Expansion<br>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)<br>* ICP-022 The drug product is a white, round, uncoated tablet<br>|

What is the study measuring?
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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 |