ICP-248 alone or with anti‑CD20 antibodies for relapsed or refractory mature B‑cell malignancies

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

This trial tests whether ICP-248 by itself or combined with an anti‑CD20 antibody is safe, tolerable, and shows signs of benefit for adults with relapsed or refractory mature B‑cell malignancies who have had prior therapies including a BTK inhibitor.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: InnoCare Pharma Inc. (industry)
• Locations: 8 sites (Plantation, Florida and 7 other locations)
• Trial ID: NCT06351527 on ClinicalTrials.gov

What this trial studies

This Phase 1, open‑label trial will give ICP‑248 as monotherapy or together with an anti‑CD20 monoclonal antibody (obinutuzumab or rituximab) to adults with relapsed or refractory CLL/SLL or mantle cell lymphoma. The study will enroll patients who have received at least two prior systemic therapies, including a Bruton's tyrosine kinase inhibitor, and have adequate organ function and ECOG performance status ≤1. Primary activities include dose escalation to define safety, tolerability, and pharmacokinetics, with secondary measures examining preliminary anti‑tumor activity. The trial is sponsored by InnoCare Pharma and is being conducted at several U.S. clinical sites.

Who should consider this trial

Good fit: Adults (age ≥18) with histologically or flow-confirmed relapsed/refractory CLL/SLL or mantle cell lymphoma who have received at least two prior systemic therapies including a BTK inhibitor, have ECOG ≤1, adequate organ and coagulation function, and measurable disease when required.

Not a fit: Patients who are treatment‑naïve, have poor organ function, ECOG >1, uncontrolled infections, or who cannot attend required visits at a participating center are unlikely to benefit from this Phase 1 trial.

Why it matters

Potential benefit: If successful, ICP‑248 could become a new treatment option that is effective and tolerable for some patients with relapsed or refractory mature B‑cell malignancies, potentially improved further when combined with an anti‑CD20 antibody.

How similar studies have performed: Combinations of targeted agents with anti‑CD20 antibodies have produced benefit in other B‑cell malignancies, but ICP‑248 is a novel agent with limited prior human data so its safety and efficacy remain unproven.

Eligibility 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.

Where this trial is running

Plantation, Florida and 7 other locations

• BRCR Medical Center — Plantation, Florida, United States (RECRUITING)
• Clinical Research Alliance — Westbury, New York, United States (RECRUITING)
• Pan American Center for Oncology Trials — San Juan, Puerto Rico (RECRUITING)
• CNE CCOHTPC of Cherkasy Regional Council — Cherkasy, Ukraine (RECRUITING)
• CNE"City Clin Hosp#4"of Dnipro City Council — Dnipro, Ukraine (RECRUITING)
• Medical Center of Limited Liability Company Arensia Exploratory Medicine — Kyiv, Ukraine (RECRUITING)
• Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC — Kyiv, Ukraine (RECRUITING)
• SI Institute of Blood Pathology and Transfusion Medicine of AMSU — Lviv, Ukraine (RECRUITING)

Study contacts

• Study coordinator: Study Director

Conditions: Mature B-cell Malignancies