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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05602363
Other study ID # C1763102
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date August 1, 2023
Est. completion date September 2027

Study information

Verified date February 2024
Source Carna Biosciences, Inc.
Contact Akinori Arimura, PhD
Phone 650-636-4603
Email clinical_us@dd.carnabio.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


Description:

This study consists of 2 parts. Dose escalation part will enroll up to 27 patients to evaluate safety profile and tolerance of AS-1763 using 3+3 design. The starting dose of AS-1763 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) and up to 35 NHL patients (Cohort 2). The first 30 patients in each cohort 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. 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 110
Est. completion date September 2027
Est. primary completion date September 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age =18 years - Provided written informed consent - Histologically confirmed B-cell malignancy, including CLL/SLL, WM, MCL, MZL, or FL. Patients must have failed or are intolerant to =2 prior lines of systemic therapy - ECOG Performance Status 0 to 2 - Absolute neutrophil count =0.75 × 10?/L - Platelet count =50 × 10?/L - Hemoglobin =8 g/dL - 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 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 AS-1763, except therapeutic monoclonal antibody treatment which must be discontinued at least 4 weeks before the start of AS-1763. 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 cytochrome P450 3A4 (CYP3A4) inhibitors or inducers - Treatment with proton pump inhibitors within 7 days before first dose of AS-1763 - Current treatment with strong P-glycoprotein inhibitors or strong breast cancer resistance protein (BCRP) inhibitors. - Refractory to transfusion support. - Major surgery within 4 weeks before planned start of AS-1763. - 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 National Cancer Institute - Common Terminology Criteria for Adverse Events (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 chimeric antigen receptor T-cell (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. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible if a compelling clinical rationale is provided by the investigator and with documented Sponsor approval. - 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 AS-1763, 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 human immunodeficiency virus (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 AS-1763 - Pregnant or lactating. - Known hypersensitivity to any component or excipient of AS-1763. - Prior treatment with AS-1763 or other noncovalent BTKi such as pirtobrutinib or nemtabrutinib

Study Design


Intervention

Drug:
AS-1763
oral tablet, twice daily

Locations

Country Name City State
United States University of Maryland Medical Center - Greenebaum Comprehensive Cancer Center Baltimore Maryland
United States University of Texas MD Anderson Cancer Center Houston Texas
United States Mount Sinai Comprehensive Cancer Center Miami Beach Florida
United States The Medical College of Wisconsin Milwaukee Wisconsin
United States UC Irvine Health Orange California
United States Moffitt Cancer Center Tampa Florida
United States Clinical Research Alliance, Inc. Westbury New York
United States University of Massachusetts Memorial Medical Center Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Carna Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Proportion of patients with BTK and PLCG2 gene mutation before and after disease progression Dose escalation, dose expansion Up to 24 cycles (1 cycle = 28 days)
Primary 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)
Primary Overall response rate (ORR) as assessed by investigator Dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Number of patients with adverse events (AEs) and clinical laboratory abnormalities Dose escalation, dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Area under the plasma concentration versus time curve (AUC) of AS-1763 Dose escalation, dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Peak Plasma Concentration (Cmax) of AS-1763 Dose escalation, dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Time to maximum plasma concentration (tmax) of AS-1763 Dose escalation, dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary ORR as assessed by investigator Dose escalation Up to 24 cycles (1 cycle = 28 days)
Secondary Best overall response as assessed by investigator Dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Duration of response as assessed by investigator Dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Progression free survival as assessed by investigator Dose expansion Up to 24 cycles (1 cycle = 28 days)
Secondary Overall survival Dose expansion Up to 4 years
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