About this trial
A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination Therapy in Patients with Mature B-cell Malignancies.This study consists of two parts: Part 1 dose-finding period and Part 2 dose expansion period.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 and ≤ 80 years.
One of the following 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: Histopathologically and/or flow cytometry-confirmed CLL/SLL; Pathologically confirmed MCL; Pathologically confirmed B-NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and lymphoplasmacytic lymphoma (LPL).
Relapsed disease or refractory disease
For subjects with B-NHL: Patients must have measurable diseasePatients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 2 and a life expectancy of ≥ 6 months.
Disqualifiers
Prior malignancy (other than the disease under study) within 2 years before study entryKnown
Central nervous system involvement by lymphoma/leukemia
Underlying medical conditions that, in the investigator's opinion, will render the administration of the investigational product hazardous or obscure the interpretation of the safety or efficacy results.
Prior autologous stem cell transplant (unless ≥ 3 months after transplant); or prior chimeric cell therapy (unless ≥ 3 months after cell infusion).
Trial design
Single group
Treatments tested in this trial
ICP-248
DrugEligible patients will receive ICP-248 orally as per the protocol, once daily for every 28 days as one treatment cycle (except for the food effect investigation phase), until progressive disease (PD), intolerable toxicity, withdrawal of consent, loss to follow-up, initiation of other anti-cancer therapy, death, or end of study, whichever occurs first.
ICP-248
DrugEligible patients will receive ICP-248 orally as specified in the treatment arm.
ICP-248+Orelabrutinib
DrugEligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.
ICP-248+Orelabrutinib
DrugEligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.
ICP-248 +Rituximab
DrugEligible patients will receive ICP-248 and Rituximab as specified in the treatment arm.
ICP-248+Orelabrutinib
DrugEligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.
ICP-248+Orelabrutinib+Rituximab
DrugEligible patients will receive ICP-248 and Orelabrutinib and Rituximab as specified in the treatment arm.
Treatment groups
7
Treatment groupsSee each treatment group below.
Trial outcomes
Primary outcomes
Maximum tolerated dose and recommended Phase 2 dose
To evaluate the safety and tolerability of ICP-248 monotherapy or combination with Orelabrutinib in the selected B-cell malignancies and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ICP-248
To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 or iwCLL2018 evaluation criteria.
To evaluate the investigator-assessed overall response rate (ORR) of ICP-248 monotherapy or combination therapy at the recommended phase II dose (RP2D) .
Secondary outcomes
Pharmacokinetic (PK) profile - Area under curve (AUC0-t)
To evaluate the AUC0-t after single administration of ICP-248 and steady state of ICP-248.
Pharmacokinetic (PK) profile - Maximum Concentration (Cmax)
To evaluate the Cmax after single administration of ICP-248 and steady state of ICP-248.
Pharmacokinetic (PK) profile - Time to maximum concentration (Tmax)
To evaluate the Tmax after single administration of ICP-248 and steady state of ICP-248.
Pharmacokinetic (PK) profile - Apparent clearance (CL/F)
To evaluate the CL/F after single administration of ICP-248 and steady state of ICP-248.
Sponsors and contacts
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