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Hematological MalignanciesPhase 1NCT05728658

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

A Phase 1 study testing ICP-248, ICP-248+Orelabrutinib and ICP-248 +Rituximab in people with Hematological Malignancies, run by Beijing InnoCare Pharma Tech Co., Ltd. at 22 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Hematological Malignancies
What is being tested?
ICP-248, ICP-248+Orelabrutinib and ICP-248 +Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
191 participants
Where
22 sitesChina
Study dates
9 Mar 2023to 30 Oct 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.
  • ≥ Grade 2 toxicity due to prior anti-cancer therapy at enrollment (except for alopecia, ANC, hemoglobin and PLT). For ANC, hemoglobin and PLT, please follow the inclusion criteria.
  • History of severe bleeding disorder
  • Known alcohol or drug dependence.
  • Presence of mental disorders or poor compliance.
  • Female patients who are pregnant or lactating.
  • Unable to swallow tablets or disease significantly affecting gastrointestinal function.
  • Hypersensitivity to the active substance or excipients of ICP-248 tablets or Orelabrutinib tablets (only applicable to subjects in cohort G/H/J/K).Severe allergic reaction or intolerance to murine monoclonal antibodies or murine products.
  • 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.

Trial locations and contacts

22 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Shuhua Yi contact

15900265415

yishuhua@ihcams.ac.cn

22 sites in 1 country

China22 sites, 22 recruiting

  • Peking University Third Hospital

    Beijing, Beijing Municipality, 100191

    Hongmei Jing

    Recruiting

  • The First Affiliated Hospital of Bengbu Medical College

    Bengbu, Anhui, 233099

    Yanli Yang

    Recruiting

  • Hunan Cancer Hospital

    Changsha, Hunan, 410000

    Yajun Li

    Recruiting

  • West China Hospital of Sichuan University

    Chengdu, Sichuan, 610000

    Liqun Zou

    Recruiting

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing, Chongqing Municipality, 400016

    Li Wang

    Recruiting

  • The Second Hospital of Dalian Medical University

    Dalian, Liaoning, 116027

    Xiuhua Sun

    Recruiting

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

    Shaoyuan Wang

    Recruiting

  • Sun Yat-Sen University Cancer Center

    Guangzhou, Guangdong, 510062

    Zhiming Li

    Recruiting

  • The First Affiliated Hospital of Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310000

    Jie Jin

    Recruiting

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, Anhui, 230022

    Jian Ge

    Recruiting

  • Shandong cancer hospital

    Jinan, Shandong, 250117

    Zengjun Li

    Recruiting

  • The First Affiliated Hospital of Nanchang University

    Nanchang, Jiangxi, 330000

    Fei Li

    Recruiting

  • Jiangxi Cancer Hospital

    Nanchang, Jiangxi, 330029

    Wuping Li

    Recruiting

  • Jiangsu Province Hospital

    Nanjing, Jiangsu, 210029

    Huayuan Zhu

    Recruiting

  • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

    Shanghai, Shanghai Municipality, 200025

    Jianqing Mi

    Recruiting

  • Shenyang Hospital Of China Medical University

    Shenyang, Liaoning, 110022

    Wei Yang

    Recruiting

  • Hematology Hospital, Chinese Academy of Medical Sciences

    Tianjin, Tianjin Municipality

    Shuhua Yi, 15900265415, yishuhua@ihcams.ac.cn

    Recruiting

  • The Central Hospital of Wuhan

    Wuhan, Hubei, 430014

    Hongxiang Wang

    Recruiting

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

    Wuhan, Hubei, 430022

    Guohui Cui

    Recruiting

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian, 361003

    Bing Xu

    Recruiting

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450008

    Keshu Zhou

    Recruiting

  • The First Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan, 450008

    Zhongxing Jiang

    Recruiting

Other trials in China

About this study

Official title: 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

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.

Being tested
ICP-248, ICP-248+Orelabrutinib, ICP-248 +Rituximab, ICP-248+Orelabrutinib+Rituximab
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ICP-248Drug

    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.

  • ICP-248Drug

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

  • ICP-248+OrelabrutinibDrug

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

  • ICP-248+OrelabrutinibDrug

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

  • ICP-248 +RituximabDrug

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

  • ICP-248+OrelabrutinibDrug

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

  • ICP-248+Orelabrutinib+RituximabDrug

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

Study groups in NCT05728658
Study groupRoleWhat they receive
Dose-Escalation Cohort - R/R CLL/SLL and R/R MCLExperimentalICP-248 was divided into 6 dose groups, and each dose group was given progressively
Receives: Drug: ICP-248
Dose-Expansion Cohort A/B/C/D/E/F (R/R CLL/SLL、R/R MCL、R/R B-NHL)ExperimentalParticipants will receive ICP-248 daily with a weekly ramp-up schedule from Cycle 1 day 1.
Receives: Drug: ICP-248
Dose-Expansion Cohort G(R/R MCL)ExperimentalParticipants 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.
Receives: Drug: ICP-248+Orelabrutinib
Dose-Expansion Cohort H(R/R MZL)ExperimentalParticipants 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.
Receives: Drug: ICP-248+Orelabrutinib
Dose-Expansion Cohort I(R/R CLL/SLL)ExperimentalParticipants 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.
Receives: Drug: ICP-248 +Rituximab
Dose-Expansion Cohort J(R/R CLL/SLL)ExperimentalParticipants 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.
Receives: Drug: ICP-248+Orelabrutinib
Dose-Expansion Cohort K(MCL)ExperimentalParticipants 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.
Receives: Drug: ICP-248+Orelabrutinib+Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 5 years

  2. To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 or iwCLL2018 evaluation criteria.

    Measured: 5 years

  3. To evaluate the investigator-assessed overall response rate (ORR) of ICP-248 monotherapy or combination therapy at the recommended phase II dose (RP2D) .

    Measured: 5 years

Secondary outcomes (11)

  1. 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.

    Measured: 5 years

  2. Pharmacokinetic (PK) profile - Maximum Concentration (Cmax)

    To evaluate the Cmax after single administration of ICP-248 and steady state of ICP-248.

    Measured: 5 years

  3. Pharmacokinetic (PK) profile - Time to maximum concentration (Tmax)

    To evaluate the Tmax after single administration of ICP-248 and steady state of ICP-248.

    Measured: 5 years

  4. Pharmacokinetic (PK) profile - Apparent clearance (CL/F)

    To evaluate the CL/F after single administration of ICP-248 and steady state of ICP-248.

    Measured: 5 years

  5. 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).

    Measured: 5 years

  6. 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).

    Measured: 5 years

  7. 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).

    Measured: 5 years

  8. 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).

    Measured: 5 years

  9. AUC of ICP-248 under different feeding conditions

    To evaluate the AUC of ICP-248 under different feeding conditions.

    Measured: 5 years

  10. Maximum Concentration (Cmax) of ICP-248 under different feeding conditions

    To evaluate the Cmax of ICP-248 under different feeding conditions.

    Measured: 5 years

  11. Time to maximum concentration (Tmax) of ICP-248 under different feeding conditions

    To evaluate the Tmax of ICP-248 under different feeding conditions.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2023
  2. Study start9 Mar 2023
  3. Primary completion30 Aug 2025 (estimated)
  4. Study completion30 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
Single blind
Who is masked
Participant
Enrolment
191 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05728658
Sponsor's protocol ID
ICP-CL-01201
Status last verified
Sep 2025
First submitted
12 Jan 2023
Last updated
8 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ICP-248, ICP-248+Orelabrutinib and ICP-248 +Rituximab in people with Hematological Malignancies, run by Beijing InnoCare Pharma Tech Co., Ltd. at 22 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Shuhua Yi (15900265415, yishuhua@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose and recommended Phase 2 dose (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05728658.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2025.

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