Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Mature B-cell Malignancies

Official title

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Patients With Mature B-cell Malignancies

Overview

Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ICP-248 as monotherapy or in combination with anti-CD20 monoclonal antibody in Mature B-cell Malignancies

Interventions

• Drug ICP-248
  ICP-248 will be administered orally once daily at escalated doses (starting dose 5/10 mg, maximum 150 mg).
• Drug Obinutuzumab (G)
  Obinutuzumab will be administered by IV infusion at a dose of 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6.
• Drug Rituximab (R)
  Rituximab will be administered by IV infusion at a dose of 375 milligrams per square meter (mg/m\^2) at Day 1 per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years.

Primary outcome measures

• DLT [Time frame: 49 days]
• Safety and tolerability of ICP-248 at different doses in B-cell malignancies [Time frame: 5 years]

Secondary outcome measures (3)

• Cmax, ss of ICP-248 [Time frame: Predose up to week 28]
• Ctrough, ss of ICP-248 [Time frame: Predose up to week 28]
• Preliminary efficacy of ICP-248 monotherapy in patients with B-cell malignancy [Time frame: 5 years]

Eligibility criteria

• Age ≥ 18.
• Subjects with histopathologically and/or flow cytometry-confirmed diseases according to the 2016 World Health Organization (WHO) classification criteria for lymphohematopoietic neoplasms or meeting the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria: relapsed or refractory CLL/SLL, relapsed or refractory MCL. Patients must have received at least two prior lines of adequate systemic therapy before study entry, and at least one prior systemic therapy should include Bruton's kinase inhibitor (BTKi).
• For subjects with R/R MCL: Patients must have measurable disease per the Lugano 2014 criteria.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 1 and a life expectancy of ≥ 6 months.
• Adequate hematologic, hepatic, renal, pulmonary and cardiac function
• Patients with basically normal coagulation function
• Patients with fertility potential and their partners need contraception
• Subjects can communicate with the investigator well and to complete the study as specified in the study.

Exclusion criteria

• Known central nervous system involvement by lymphoma/leukemia.
• Known or suspected history of Richter's transformation.
• Prior autologous stem cell transplant (unless ≥ 3 months since transplant); or prior chimeric cell therapy (unless ≥ 3 months since cell infusion).
• A history of allogeneic stem cell transplantation.
• An interval of less than 5 half-lives from the last dose of a strong CYP3A or CYP2C8 inhibitor or inducer (chemical agent, herbal medicine and dietary supplement) to the first dose of the investigational product, or a plan to use concurrently medications, dietary supplements or food (e.g., grapefruit or grapefruit juice) with strong CYP3A or CYP2C8 inhibitory or inductive effect during study participation
• Presence of active infection that currently requires intravenous systemic anti-infective therapy.
• History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
• History of significant cardiovascular disease
• Patients with previous or concomitant central nervous system disorders
• Grade 2 or above toxicity due to prior anti-cancer therapy at screening
• Known alcohol or drug dependence
• Unable to swallow tablets or presence of disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Ukraine · 5 centers

• CNE CCOHTPC of Cherkasy Regional Council — Cherkasy
• CNE"City Clin Hosp#4"of Dnipro City Council — Dnipro
• Medical Center of Limited Liability Company Arensia Exploratory Medicine — Kyiv
• Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC — Kyiv
• SI Institute of Blood Pathology and Transfusion Medicine of AMSU — Lviv

United States · 2 centers

• BRCR Medical Center — Plantation
• Clinical Research Alliance — Westbury

Puerto Rico · 1 center

• Pan American Center for Oncology Trials — San Juan

Identifiers

NCT: NCT06351527 · ICP-CL-01202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗