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

Hematological Malignancies Clinical Trial

Official title:

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ICP-248 in Patients With Mature B-cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05728658
• Other study ID #: ICP-CL-01201
• Status: Recruiting
• Phase: Phase 1
• Start date: March 9, 2023
• Est. completion date: October 30, 2026

Study information

• Verified date: April 2024
• Source: Beijing InnoCare Pharma Tech Co., Ltd.
• Contact: Shuhua Yi
• Phone: 15900265415
• Email: yishuhua[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase I study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ICP-248 in patients with mature B-cell malignancies. This study consists of two parts: Part 1 dose-finding period and Part 2 dose expansion period

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: October 30, 2026
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age = 18 and = 80 years.

2. 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).

3. Relapsed disease or refractory disease

4. 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.

5. Adequate hematologic function.

6. Patients with basically normal coagulation function.

7. Patients with adequate hepatic, renal, pulmonary and cardiac functions.

8. 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.

9. 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.

10. Subjects are able to communicate with the investigator well and to complete the study as specified in the study.

11. 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).

12. Subjects with CLL/SLL must have an indication for treatment as judged by the investigator.

Exclusion Criteria:

1. Prior malignancy (other than the disease under study) within 2 years before study entryKnown

2. Central nervous system involvement by lymphoma/leukemia

3. 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.

4. Prior autologous stem cell transplant (unless = 3 months after transplant); or prior chimeric cell therapy (unless = 3 months after cell infusion).

5. 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.

6. A history of allogeneic stem cell transplantation.

7. Anti-cancer therapy within 14 days prior to the first dose of the investigational product

8. An interval of less than 5 half-lives from the last dose of a strong CYP3A or CYP2C8 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 or CYP2C8 inhibitory or inductive effect during study participation.

9. 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.

10. 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).

11. Presence of active infection that currently requires intravenous systemic anti-infective therapy.

12. Patients with active hepatitis B or C virus infection.

13. History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.

14. History of significant cardiovascular disease

15. Patients with previous or concomitant central nervous system disordersHistory or current evidence of severe interstitial lung disease.

16. = 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.

17. History of severe bleeding disorder

18. Known alcohol or drug dependence.

19. Presence of mental disorders or poor compliance.

20. Female patients who are pregnant or lactating.

21. Unable to swallow tablets or disease significantly affecting gastrointestinal function.

22. Hypersensitivity to the active substance or excipients of ICP-248 tablets.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Drug:
• ICP-248
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.

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Shandong cancer hospital	Jinan	Shandong
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shenyang Hospital Of China Medical University	Shenyang	Liaoning
China	Hematology Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	The Central Hospital of Wuhan	Wuhan	Hubei
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing InnoCare Pharma Tech Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose and recommended Phase 2 dose	To evaluate the safety and tolerability of ICP-248 monotherapy in the selected B-cell malignancies and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ICP-248 monotherapy	5 years
Primary	To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 or iwCLL2018 evaluation criteria.		5 years
Secondary	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
Secondary	Pharmacokinetic (PK) profile - Maximum Concentration (Cmax)	To evaluate the Cmax after single administration of ICP-248 and steady state of ICP-248.	5 years
Secondary	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
Secondary	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
Secondary	Preliminary efficacy - Overall response rate (ORR)	To evaluate the preliminary efficacy of ICP-248 monotherapy in the evaluated disease types as measured by investigator-assessed overall response rate (ORR)	5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	AUC of ICP-248 under different feeding conditions	To evaluate the AUC of ICP-248 under different feeding conditions.	5 years
Secondary	Maximum Concentration (Cmax) of ICP-248 under different feeding conditions	To evaluate the Cmax of ICP-248 under different feeding conditions.	5 years
Secondary	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