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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
191
Eligible 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.
Eligible patients will receive ICP-248 orally as specified in the treatment arm.
Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.
The First Affiliated Hospital of Bengbu Medical College
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
Time frame: 5 years
To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 or iwCLL2018 evaluation criteria.
Time frame: 5 years
To evaluate the investigator-assessed overall response rate (ORR) of ICP-248 monotherapy or combination therapy at the recommended phase II dose (RP2D) .
Time frame: 5 years
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.
Time frame: 5 years
Pharmacokinetic (PK) profile - Maximum Concentration (Cmax)
To evaluate the Cmax after single administration of ICP-248 and steady state of ICP-248.
Time frame: 5 years
Pharmacokinetic (PK) profile - Time to maximum concentration (Tmax)
To evaluate the Tmax after single administration of ICP-248 and steady state of ICP-248.
Time frame: 5 years
Pharmacokinetic (PK) profile - Apparent clearance (CL/F)
To evaluate the CL/F after single administration of ICP-248 and steady state of ICP-248.
Time frame: 5 years
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Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.
Eligible patients will receive ICP-248 and Rituximab as specified in the treatment arm.
Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.
Eligible patients will receive ICP-248 and Orelabrutinib and Rituximab as specified in the treatment arm.
Bengbu, Anhui, China
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
RECRUITINGPeking University Third Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
RECRUITINGFujian Medical University Union Hospital
Fuzhou, Fujian, China
RECRUITINGThe First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGThe First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
RECRUITINGThe Central Hospital of Wuhan
Wuhan, Hubei, China
RECRUITING...and 12 more locations
Preliminary efficacy - Complete response rate (CRR)
To evaluate the preliminary efficacy of ICP-248 monotherapy in the evaluated disease types as measured by investigator-assessed complete response rate (CRR).
Time frame: 5 years
Preliminary efficacy - Progression-free survival (PFS)
To evaluate the preliminary efficacy of ICP-248 monotherapy in the evaluated disease types as measured by investigator-assessed progression-free survival (PFS).
Time frame: 5 years
Preliminary efficacy - Duration of response (DOR)
To evaluate the preliminary efficacy of ICP-248 monotherapy in the evaluated disease types as measured by investigator-assessed duration of response (DOR).
Time frame: 5 years
Preliminary efficacy - Overall survival (OS)
To evaluate the preliminary efficacy of ICP-248 monotherapy in the evaluated disease types as measured by investigator-assessed overall survival (OS).
Time frame: 5 years
AUC of ICP-248 under different feeding conditions
To evaluate the AUC of ICP-248 under different feeding conditions.
Time frame: 5 years
Maximum Concentration (Cmax) of ICP-248 under different feeding conditions
To evaluate the Cmax of ICP-248 under different feeding conditions.
Time frame: 5 years
Time to maximum concentration (Tmax) of ICP-248 under different feeding conditions
To evaluate the Tmax of ICP-248 under different feeding conditions.
Time frame: 5 years