Evaluating ICP-248 for treating mature B-cell cancers

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 is testing a new treatment called ICP-248, alone and with another drug, to see if it can help people with mature B-cell cancers.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 191 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd. (Industry-sponsored)
• Drugs / interventions: Rituximab, Orelabrutinib
• Locations: 22 sites (Bengbu, Anhui and 21 other locations)
• Trial ID: NCT05728658 on ClinicalTrials.gov

What this trial studies

This Phase I study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ICP-248, both as a standalone treatment and in combination with Orelabrutinib, for patients with mature B-cell malignancies. The study is divided into two parts: a dose-finding period followed by a dose expansion period. Participants will be closely monitored to determine the optimal dosing and effectiveness of the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 80 with confirmed mature B-cell malignancies who have relapsed or refractory disease.

Not a fit: Patients with early-stage or untreated mature B-cell malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed or refractory mature B-cell malignancies.

How similar studies have performed: Other studies have shown promise in targeting similar malignancies with novel therapies, indicating potential for success in this approach.

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 Orelabrutinib Or within 12 months after the last dose of Rituximab (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/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.

Where this trial is running

Bengbu, Anhui and 21 other locations

• The First Affiliated Hospital of Bengbu Medical College — Bengbu, Anhui, China (Recruiting)
• The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (Recruiting)
• Peking University Third Hospital — Beijing, Beijing Municipality, China (Recruiting)
• The First Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Recruiting)
• Fujian Medical University Union Hospital — Fuzhou, Fujian, China (Recruiting)
• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (Recruiting)
• Sun Yat-Sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• The Central Hospital of Wuhan — Wuhan, Hubei, China (Recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Recruiting)
• Jiangxi Cancer Hospital — Nanchang, Jiangxi, China (Recruiting)
• The Second Hospital of Dalian Medical University — Dalian, Liaoning, China (Recruiting)
• Shenyang Hospital Of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Shandong cancer hospital — Jinan, Shandong, China (Recruiting)
• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, 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, China (Recruiting)

Study contacts

• Study coordinator: Shuhua Yi

Conditions Hematological Malignancies