Part 1：r/r B-cell Malignancies, Part 2：B-cell Malignancies
Conditions
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).
Interventions
ICP-022 The drug product is a white, round, uncoated tablet
Sponsors
Beijing InnoCare Pharma Tech Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 Dose Escalation：The maximum tolerated dose (MTD) | Incidence of dose limiting toxicities (DLTs) up to 28 days | To determine the maximum tolerated dose (MTD) |
| Part 2 Dose Expansion：ORR | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 Dose Escalation：T1/2 | Up to 2 years | Elimination half-life |
| Part 1 Dose Escalation：Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability] | 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 | Up to 2 years | Duration of response |
| Part 2 Dose Expansion：Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability] | 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 | Up to 2 years | Objective response rate |
Countries
Israel, Poland, Ukraine, United States
Outcome results
None listed