Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Mature B-cell Malignancies

InnoCare Pharma

Status and phase: Enrolling; Phase 1

Conditions: Mature B-cell Malignancies

Treatments: Drug: ICP-248; Drug: Rituximab (R); Drug: Obinutuzumab (G)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06351527

ICP-CL-01202

Details and patient eligibility

About

Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ICP-248 as monotherapy or in combination with anti-CD20 monoclonal antibody in Mature B-cell Malignancies

Enrollment: 78 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

1. Age ≥ 18.
2. Subjects with 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: relapsed or refractory CLL/SLL, relapsed or refractory MCL. Patients must have received at least two prior lines of adequate systemic therapy before study entry, and at least one prior systemic therapy should include Bruton's kinase inhibitor (BTKi).
3. For subjects with R/R MCL: Patients must have measurable disease per the Lugano 2014 criteria.
4. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 1 and a life expectancy of ≥ 6 months.
5. Adequate hematologic, hepatic, renal, pulmonary and cardiac function
6. Patients with basically normal coagulation function
7. Patients with fertility potential and their partners need contraception
8. Subjects can communicate with the investigator well and to complete the study as specified in the study.

Exclusion Criteria:

1. Known central nervous system involvement by lymphoma/leukemia.
2. Known or suspected history of Richter's transformation.
3. Prior autologous stem cell transplant (unless ≥ 3 months since transplant); or prior chimeric cell therapy (unless ≥ 3 months since cell infusion).
4. A history of allogeneic stem cell transplantation.
5. An interval of less than 5 half-lives from the last dose of a strong CYP3A or CYP2C8 inhibitor or inducer (chemical agent, herbal 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
6. Presence of active infection that currently requires intravenous systemic anti-infective therapy.
7. History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
8. History of significant cardiovascular disease
9. Patients with previous or concomitant central nervous system disorders
10. Grade 2 or above toxicity due to prior anti-cancer therapy at screening
11. Known alcohol or drug dependence
12. Unable to swallow tablets or presence of disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 4 patient groups

Dose-Escalation Cohort - CLL/SLL and MCL

Experimental group

Description:

Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose. Cycles will comprise 28 days.

Treatment:

Drug: ICP-248

Dose-Expansion Cohort A - CLL/SLL

Experimental group

Description:

Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose and obinutuzumab for 6 cycles. Cycles will comprise 28 days.

Treatment:

Drug: Obinutuzumab (G)

Drug: ICP-248

Dose-Expansion Cohort B - MCL

Experimental group

Description:

Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose. Cycles will comprise 28 days.

Treatment:

Drug: ICP-248

Dose-Expansion Cohort C - MCL

Experimental group

Description:

Participants will receive ICP-248 daily from an initial dose of 5/10 mg to the target dose and Rituximab for 18 cycles. Cycles will comprise 28 days.

Treatment:

Drug: Rituximab (R)

Drug: ICP-248