The Study of ICP-248 in Patients With Mature B-cell Malignancies

NCT05728658 | Recruiting Phase 1

• 1 other identifier: ICP-CL-01201
• Study Type: interventional
• Target: 191
• Locations: 1 country
• Sites: 22

Brief Summary

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.

Conditions

Hematological Malignancies

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (11)

• Pharmacokinetic (PK) profile - Area under curve (AUC0-t)

  5 years

• Pharmacokinetic (PK) profile - Maximum Concentration (Cmax)

  5 years

• Pharmacokinetic (PK) profile - Time to maximum concentration (Tmax)

  5 years

• Pharmacokinetic (PK) profile - Apparent clearance (CL/F)

  5 years

• Preliminary efficacy - Complete response rate (CRR)

  5 years

Study Arms (7)

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

Drug: ICP-248

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.

Drug: ICP-248

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.

Drug: ICP-248+Orelabrutinib

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.

Drug: ICP-248+Orelabrutinib

Dose-Expansion Cohort I(R/R CLL/SLL)

EXPERIMENTAL

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.

Drug: ICP-248 +Rituximab

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.

Drug: ICP-248+Orelabrutinib

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.

Drug: ICP-248+Orelabrutinib+Rituximab

Interventions

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.

Dose-Escalation Cohort - R/R CLL/SLL and R/R MCL

ICP-248+Orelabrutinib DRUG

Eligible patients will receive ICP-248 and Orelabrutinib as specified in the treatment arm.

Dose-Expansion Cohort G(R/R MCL)

ICP-248 +Rituximab DRUG

Eligible patients will receive ICP-248 and Rituximab as specified in the treatment arm.

Dose-Expansion Cohort I(R/R CLL/SLL)

ICP-248+Orelabrutinib+Rituximab DRUG

Eligible patients will receive ICP-248 and Orelabrutinib and Rituximab as specified in the treatment arm.

Dose-Expansion Cohort K(MCL)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Adequate hematologic function.
• Patients with basically normal coagulation function.
• Patients with adequate hepatic, renal, pulmonary and cardiac functions.
• CLL/SLL Patients with an absolute lymphocyte count ≥ 50 x 109/L and any lymph nodes ≥ 5 cm in the long diameter or CLL/SLL or B-NHL patients with any lymph nodes ≥ 10 cm in the long diameter will be enrolled in the study after weighing the risks and benefits with the sponsor's MM.
• Female patients of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first dose of the investigational product; patients of childbearing potential (males and females) must agree to use a reliable birth control method (hormonal or barrier method or abstinence) with their partners from signing the ICF until 90 days after the last dose.The last ICP- 248 dose or within one month after the last dose of Orelabrutinib Or within 12 months after the last dose of Rituximab (whichever is longer).
• Subjects are able to communicate with the investigator well and to complete the study as specified in the study.
• Before the trial, the subjects shall understand the nature, significance, possible benefits, inconveniences and potential risks, as well as the study procedures of the trial in detail and voluntarily sign the written Informed Consent Form (ICF).
• Subjects with CLL/SLL must have an indication for treatment as judged by the investigator.

You may not qualify if:

• 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).
• Received a BCL-2 inhibitor prior to initial use of the investigational drug and did not achieve disease remission or disease recurrence/progression on treatment; Disease recurrence/progression after stopping or ending BCL-2 inhibitor therapy is acceptable.
• A history of allogeneic stem cell transplantation.
• Anti-cancer therapy within 14 days prior to the first dose of the investigational product
• An interval of less than 5 half-lives from the last dose of a strong CYP3A inhibitor or inducer (chemical agent, traditional Chinese 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 inhibitory or inductive effect during study participation.
• Patients who have undergone major organ surgery (excluding aspiration biopsy) or significant trauma within 28 days prior to the first dose of the investigational product, or who require elective surgery during the trial.
• Patients who have received a live attenuated vaccine within 28 days prior to the first dose of the investigational product (except for vaccination to prevent a major public health event).
• Presence of active infection that currently requires intravenous systemic anti-infective therapy.
• Patients with active hepatitis B or C virus infection.
• 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 disordersHistory or current evidence of severe interstitial lung disease.

Sponsors & Collaborators

• Beijing InnoCare Pharma Tech Co., Ltd.: lead

Study Sites (22)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233099, China

RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510062, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450008, China

RECRUITING

The Central Hospital of Wuhan

Wuhan, Hubei, 430014, China

RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

RECRUITING

Jiangxi Cancer Hospital

Nanchang, Jiangxi, 330029, China

RECRUITING

The Second Hospital of Dalian Medical University

Dalian, Liaoning, 116027, China

RECRUITING

Shenyang Hospital Of China Medical University

Shenyang, Liaoning, 110022, China

RECRUITING

Shandong cancer hospital

Jinan, Shandong, 250117, China

RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

RECRUITING

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

RECRUITING

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Shuhua Yi

CONTACT

15900265415; yishuhua@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: February 15, 2023
• Study Start: March 9, 2023
• Primary Completion: August 30, 2025
• Study Completion (Estimated): October 30, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (22)