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

December 9, 2025 updated by: Carna Biosciences, Inc.

A Phase 1b Study of Oral AS-1763 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study consists of 2 parts.

Dose escalation part will enroll up to 27 patients to evaluate safety profile and tolerance of docirbrutinib using 3+3 design. The starting dose of docirbrutinib in oral tablet form is 100 mg twice daily (200 mg/day). Dose escalation will continue up to the planned maximum dose level or until the maximum tolerated dose (MTD) has been identified.

Dose expansion part will enroll up to 48 CLL/SLL patients (Cohort 1), up to 35 NHL patients (Cohort 2), and up to 10 patients with prior pirtobrutinib treatment for an approved indication (Cohort 3). The first 30 patients in each Cohort 1 or 2 will be allocated to three dose levels (n=10 at each dose level) which will be selected based on the data from dose escalation. Preliminary efficacy and safety data from the first 30 patients in one of cohorts will be used to identify the provisional recommended Phase 2 dose (RP2D) level. Thereafter, up to a further 18 patients for Cohort 1 and up to a further 5 patients for Cohort 2 will be enrolled and allocated to the provisional RP2D level. Cohort 3 will be enrolled in parallel with Cohorts 1 and 2 and will be allocated to up to two dose levels (either n=10 at a single dose level or n=5 at each of 2 dose levels).

Study assessments will continue for 24 cycles (1 cycle = 28 days) or until disease progression, occurrence of unacceptable toxicity, or discontinuation because of other reasons. Patients will then be followed for survival status for a further 2 years.

RP2D will be determined based on all the data generated in the study.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health
        • Contact:
        • Principal Investigator:
          • Catherine Coombs, MD
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Recruiting
        • Mount Sinai Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Jacqueline Barrientos, MD
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Javier Pinilla-Ibarz, MD PhD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60661
        • Recruiting
        • Northwestern Memorial Hospital
        • Principal Investigator:
          • Shuo Ma, MD PhD
        • Contact:
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Recruiting
        • American Oncology Partners
        • Principal Investigator:
          • Sunil Babu, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Medical Center - Greenebaum Comprehensive Cancer Center
        • Contact:
          • Nikki M Glynn-Cunningham, MS
          • Phone Number: 410-328-7996
          • Email: nglynn@umm.edu
        • Principal Investigator:
          • Seung Tae Lee, MD PhD
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • University of Massachusetts Memorial Medical Center
        • Contact:
        • Principal Investigator:
          • Andrew J Gillis-Smith, MD
    • New York
      • Westbury, New York, United States, 11590
        • Recruiting
        • Optum Medical Care PC
        • Contact:
        • Principal Investigator:
          • Jonathan Goldberg, MD
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University
        • Principal Investigator:
          • Danielle Brander, MD
        • Contact:
    • Ohio
      • Maumee, Ohio, United States, 43537
        • Recruiting
        • Taylor Cancer Research Center
        • Principal Investigator:
          • John Nemunaitis, MD
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Nitin Jain, MD
      • Houston, Texas, United States, 77030
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53266
        • Recruiting
        • The Medical College of Wisconsin
        • Principal Investigator:
          • Nirav Shah, MD
        • Contact:
          • Medical College of Wisconsin Cancer Center Clinical Trials Office
          • Phone Number: 414-805-8900
          • Email: cccto@mcw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months before planned start of docirbrutinib, or prolongation of the QT interval corrected for heart rate using Fridericia's Formula (QTcF) >470 msec on at least 2 of 3 consecutive ECGs, and mean QTcF >470 msec on all 3 ECGs, during Screening
  • Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
  • Positive for HIV. For patients with unknown HIV status, HIV testing will be performed at Screening
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of docirbrutinib
  • Pregnant or lactating.
  • Known hypersensitivity to any component or excipient of docirbrutinib
  • Prior treatment with docirbrutinib
  • Dose Escalation and Cohort 3 patients: prior treatment with noncovalent BTKi except pirtobrutinib (Jaypirca)
  • Dose Expansion Cohort 1 and Cohort 2 patients: prior treatment with any noncovalent BTKi

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation

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
oral tablet, twice daily
Other Names:
  • AS-1763
Experimental: Dose Expansion

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
oral tablet, twice daily
Other Names:
  • AS-1763

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with dose limiting toxicities (DLTs) and determination of maximum tolerated dose (MTD)
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation
Up to 24 cycles (1 cycle = 28 days)
Overall response rate (ORR) as assessed by investigator
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose expansion
Up to 24 cycles (1 cycle = 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events (AEs) and clinical laboratory abnormalities
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation, dose expansion
Up to 24 cycles (1 cycle = 28 days)
Overall survival
Time Frame: Up to 4 years
Dose expansion
Up to 4 years
ORR as assessed by investigator
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation
Up to 24 cycles (1 cycle = 28 days)
Best overall response as assessed by investigator
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose expansion
Up to 24 cycles (1 cycle = 28 days)
Duration of response as assessed by investigator
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose expansion
Up to 24 cycles (1 cycle = 28 days)
Progression free survival as assessed by investigator
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose expansion
Up to 24 cycles (1 cycle = 28 days)
Area under the plasma concentration versus time curve (AUC) of docirbrutinib
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation, dose expansion
Up to 24 cycles (1 cycle = 28 days)
Peak Plasma Concentration (Cmax) of docirbrutinib
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation, dose expansion
Up to 24 cycles (1 cycle = 28 days)
Time to maximum plasma concentration (tmax) of docirbrutinib
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation, dose expansion
Up to 24 cycles (1 cycle = 28 days)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with BTK and PLCG2 gene mutation before and after disease progression
Time Frame: Up to 24 cycles (1 cycle = 28 days)
Dose escalation, dose expansion
Up to 24 cycles (1 cycle = 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Carna Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

October 24, 2022

First Submitted That Met QC Criteria

October 26, 2022

First Posted (Actual)

November 2, 2022

Study Record Updates

Last Update Posted (Actual)

December 10, 2025

Last Update Submitted That Met QC Criteria

December 9, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C1763102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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