AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma

NCT05602363 | Recruiting Phase 1 FDA Drug

• 1 other identifier: C1763102
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 13

Brief Summary

This is an open-label, multi-center Phase 1b clinical study of oral AS-1763 (docirbrutinib) in patients with CLL/SLL or B-cell NHL who have failed or are intolerant to ≥2 lines of systemic therapy.

Conditions

B-cell Malignancy; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Follicular Lymphoma; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Number of patients with dose limiting toxicities (DLTs) and determination of maximum tolerated dose (MTD)

  Dose escalation

  Up to 24 cycles (1 cycle = 28 days)

• Overall response rate (ORR) as assessed by investigator

  Dose expansion

  Up to 24 cycles (1 cycle = 28 days)

Secondary Outcomes (9)

• Number of patients with adverse events (AEs) and clinical laboratory abnormalities

  Up to 24 cycles (1 cycle = 28 days)

• Area under the plasma concentration versus time curve (AUC) of docirbrutinib

  Up to 24 cycles (1 cycle = 28 days)

• Peak Plasma Concentration (Cmax) of docirbrutinib

  Up to 24 cycles (1 cycle = 28 days)

• Time to maximum plasma concentration (tmax) of docirbrutinib

  Up to 24 cycles (1 cycle = 28 days)

• ORR as assessed by investigator

  Up to 24 cycles (1 cycle = 28 days)

Other Outcomes (1)

• Proportion of patients with BTK and PLCG2 gene mutation before and after disease progression

  Up to 24 cycles (1 cycle = 28 days)

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Dose escalation (3+3 design) and determination of MTD and DLTs CLL/SLL or B-cell NHL patients will self-administer docirbrutinib oral tablet at multiple dose levels twice daily for 24 cycles (1 cycle = 28 days).

Drug: Docirbrutinib

Dose Expansion

EXPERIMENTAL

Cohort 1: CLL/SLL patients, Cohort 2: B-cell NHL patients, Cohort 3: CLL/SLL or B-cell NHL patients with prior treatment with pirtobrutinib (Jaypirca) for an approved indication Patients will self-administer docirbrutinib oral tablet for 24 cycles (1 cycle = 28 days). Dose levels will be determined based on the result of dose escalation part.

Drug: Docirbrutinib

Interventions

Docirbrutinib DRUG

oral tablet, twice daily

Also known as: AS-1763

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Provided written informed consent
• Histologically confirmed B-cell malignancy, including CLL/SLL, WM, MCL, MZL, or FL
• Patients with SLL, MCL, MZL, and FL: at least 1 radiographically measurable lesion
• Failed or are intolerant to ≥2 prior lines of systemic therapy
• ECOG Performance Status 0 to 2
• Adequate hematologic status (ie, absolute neutrophil count ≥0.75 × 10⁹/L, platelet count ≥50 × 10⁹/L, hemoglobin ≥8 g/dL) not requiring transfusion support or growth factors
• Adequate hepatic function
• Adequate renal function
• Ability to swallow tablets and comply with study requirements for the duration of study participation
• Male and female patients of reproductive potential: Willing to observe conventional and effective birth control methods
• Male patients: agree not to donate sperm during and for 6 months after the study
• Dose Expansion Cohort 3 patients: prior treatment with pirtobrutinib (Jaypirca) for an approved indication

You may not qualify if:

• Transformed disease (eg, Richter's transformation) prior to or during Screening
• Investigational agent or anticancer therapy within 5 half-lives before the planned start of docirbrutinib, except therapeutic monoclonal antibody treatment which must be discontinued at least 4 weeks before the start of docirbrutinib
• Current treatment with investigational therapy or planned investigational therapy which would be concurrent with this study
• Requiring therapeutic anticoagulation with warfarin
• Current treatment with certain strong CYP3A4 inhibitors or inducers
• Treatment with proton pump inhibitors within 7 days before first dose of docirbrutinib
• Current treatment with strong P-glycoprotein inhibitors or strong BCRP inhibitors
• Refractory to transfusion support
• Major surgery within 4 weeks before planned start of docirbrutinib
• Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 2 at the time of starting study treatment except for alopecia
• History of allogeneic or autologous stem cell transplant or CAR-T therapy within the last 30 days
• Active second malignancy unless in remission with life expectancy \>2 years
• Known central nervous system (CNS) involvement by systemic lymphoma
• Active uncontrolled autoimmune cytopenia (eg, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) where new therapy introduced or concomitant therapy escalated within the 4 weeks before study enrollment is required to maintain adequate blood counts

Sponsors & Collaborators

• Carna Biosciences, Inc.: lead

Study Sites (13)

UC Irvine Health

Orange, California, 92868, United States

RECRUITING

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, 60661, United States

RECRUITING

American Oncology Partners

Fort Wayne, Indiana, 46804, United States

RECRUITING

University of Maryland Medical Center - Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

RECRUITING

Optum Medical Care PC

Westbury, New York, 11590, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

Oncology Consultants

Houston, Texas, 77030, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53266, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma; Lymphoma, B-Cell

Central Study Contacts

Akinori Arimura, PhD

CONTACT

650-636-4603; clinical_us@dd.carnabio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: November 2, 2022
• Study Start: August 1, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)