Clinical trial NCT05728658: The Study of ICP-248 in Patients with Mature B-cell Malignancies
Official title: A Phase I Study to Evaluate the Safety, Tolerability,harmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ICP-248 Monotherapy or Combination with Orelabrutinib in Patients with Mature B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hematological Malignancies
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-02-15
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ICP-248 monotherapy or combination with Orelabrutinib in Patients with Mature B-cell Malignancies. This study consists of two parts: Part 1 dose-finding period and Part 2 dose expansion period.


Eligibility criteria: 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.The last ICP- 248 dose or within one month after the last dose of Obutinib (whichever is longer).
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 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.
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 or Orelabrutinib tablets (only applicable to subjects in cohort G/H).

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.

Primary outcomes:
measure: Maximum tolerated dose and recommended Phase 2 dose
timeFrame: 5 years
measure: To investigate the incidence, nature and severity of adverse events (AE) according to NCI-CTCAE V5.0 or iwCLL2018 evaluation criteria.
timeFrame: 5 years
Secondary outcomes:
measure: Pharmacokinetic (PK) profile - Area under curve (AUC0-t)
timeFrame: 5 years
measure: Pharmacokinetic (PK) profile - Maximum Concentration (Cmax)
timeFrame: 5 years
measure: Pharmacokinetic (PK) profile - Time to maximum concentration (Tmax)
timeFrame: 5 years
measure: Pharmacokinetic (PK) profile - Apparent clearance (CL/F)
timeFrame: 5 years
measure: Preliminary efficacy - Overall response rate (ORR)
timeFrame: 5 years
measure: Preliminary efficacy - Complete response rate (CRR)
timeFrame: 5 years
measure: Preliminary efficacy - Progression-free survival (PFS)
timeFrame: 5 years
measure: Preliminary efficacy - Duration of response (DOR)
timeFrame: 5 years
measure: Preliminary efficacy - Overall survival (OS)
timeFrame: 5 years
measure: AUC of ICP-248 under different feeding conditions
timeFrame: 5 years
measure: Maximum Concentration (Cmax) of ICP-248 under different feeding conditions
timeFrame: 5 years
measure: Time to maximum concentration (Tmax) of ICP-248 under different feeding conditions
timeFrame: 5 years
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: The Central Hospital of Wuhan
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shenyang Hospital Of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong cancer hospital
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Hematology Hospital, Chinese Academy of Medical Sciences
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: