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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-Escalation Cohort - R/R CLL/SLL and R/R MCL | Experimental | ICP-248 was divided into 6 dose groups, and each dose group was given progressively |
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| Dose-Expansion Cohort A/B/C/D/E/F (R/R CLL/SLL、R/R MCL、R/R B-NHL) | Experimental | Participants will receive ICP-248 daily with a weekly ramp-up schedule from Cycle 1 day 1. |
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| Dose-Expansion Cohort G(R/R MCL) | Experimental | Participants will receive ICP-248 daily with a ramp-up phase, and will receive Orelabrutinib 150 mg daily, 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. |
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| Dose-Expansion Cohort H(R/R MZL) | Experimental | Participants will receive ICP-248 daily with a weekly ramp-up schedule and Orelabrutinib 150 mg daily from Cycle 1 day 1, 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. |
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| Dose-Expansion Cohort I(R/R CLL/SLL) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ICP-248 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 5 years |
| To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 or iwCLL2018 evaluation criteria. | 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) . | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 years |
| Pharmacokinetic (PK) profile - Maximum Concentration (Cmax) |
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Inclusion Criteria:
Exclusion Criteria:
23 Invasive mantle cell lymphoma, such as mother cell subtypes, polymorphic subtypes, or Ki-67 proliferation index>50%, must be discussed with the sponsor's medical monitor regarding patient benefits and risks before being included in this study.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shuhua Yi | Contact | 15900265415 | yishuhua@ihcams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Bengbu Medical College | Recruiting | Bengbu | Anhui | 233099 | China |
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Participants will receive ICP-248 daily with a weekly ramp-up schedule from Cycle 1 day 1, and will receive 375 mg/m2 Rituximab on day 1 of each cycle from C1 to C6,or 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.
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| Dose-Expansion Cohort J(R/R CLL/SLL) | Experimental | Participants will receive Orelabrutinib 150 mg daily from cycle 1 day 1, and will receive ICP-248 daily with a daily ramp-up schedule from Cycle 3 day 1, 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. |
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| Dose-Expansion Cohort K(MCL) | Experimental | Participants will receive Orelabrutinib 150 mg daily from cycle 1 day 1, and Rituximab 375 mg per square meter was infused intravenously on day 1 of each cycle from C1-6 and on day 1 of every two cycles from C7D1 onwards, and ICP-248 daily with a weekly ramp-up schedule from cycle 3 day 1. The treatment will continue up to a maximum of 24 cycles, or 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. |
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| ICP-248 | Drug | Eligible patients will receive ICP-248 orally as specified in the treatment arm. |
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| ICP-248+Orelabrutinib | Drug | Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm. |
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| ICP-248+Orelabrutinib | Drug | Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm. |
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| ICP-248 +Rituximab | Drug | Eligible patients will receive ICP-248 and Rituximab as specified in the treatment arm. |
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| ICP-248+Orelabrutinib | Drug | Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm. |
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| ICP-248+Orelabrutinib+Rituximab | Drug | Eligible patients will receive ICP-248 and Orelabrutinib and Rituximab as specified in the treatment arm. |
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To evaluate the Cmax after single administration of ICP-248 and steady state of ICP-248.
| 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. | 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. | 5 years |
| 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). | 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). | 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). | 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). | 5 years |
| AUC of ICP-248 under different feeding conditions | To evaluate the AUC of ICP-248 under different feeding conditions. | 5 years |
| Maximum Concentration (Cmax) of ICP-248 under different feeding conditions | To evaluate the Cmax of ICP-248 under different feeding conditions. | 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. | 5 years |
| The First Affiliated Hospital of Anhui Medical University | Recruiting | Hefei | Anhui | 230022 | China |
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| Peking University Third Hospital | Recruiting | Beijing | Beijing Municipality | 100191 | China |
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| The First Affiliated Hospital of Chongqing Medical University | Recruiting | Chongqing | Chongqing Municipality | 400016 | China |
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| Fujian Medical University Union Hospital | Recruiting | Fuzhou | Fujian | 350001 | China |
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| The First Affiliated Hospital of Xiamen University | Recruiting | Xiamen | Fujian | 361003 | China |
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| Sun Yat-Sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510062 | China |
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| Henan Cancer Hospital | Recruiting | Zhengzhou | Henan | 450008 | China |
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| The First Affiliated Hospital of Zhengzhou University | Recruiting | Zhengzhou | Henan | 450008 | China |
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| The Central Hospital of Wuhan | Recruiting | Wuhan | Hubei | 430014 | China |
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| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Recruiting | Wuhan | Hubei | 430022 | China |
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| Hunan Cancer Hospital | Recruiting | Changsha | Hunan | 410000 | China |
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| Jiangsu Province Hospital | Recruiting | Nanjing | Jiangsu | 210029 | China |
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| The First Affiliated Hospital of Nanchang University | Recruiting | Nanchang | Jiangxi | 330000 | China |
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| Jiangxi Cancer Hospital | Recruiting | Nanchang | Jiangxi | 330029 | China |
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| The Second Hospital of Dalian Medical University | Recruiting | Dalian | Liaoning | 116027 | China |
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| Shenyang Hospital Of China Medical University | Recruiting | Shenyang | Liaoning | 110022 | China |
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| Shandong cancer hospital | Recruiting | Jinan | Shandong | 250117 | China |
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| Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Recruiting | Shanghai | Shanghai Municipality | 200025 | China |
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| West China Hospital of Sichuan University | Recruiting | Chengdu | Sichuan | 610000 | China |
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| Hematology Hospital, Chinese Academy of Medical Sciences | Recruiting | Tianjin | Tianjin Municipality | China |
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| The First Affiliated Hospital of Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | 310000 | China |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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