Trial Title:
AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma
NCT ID:
NCT05602363
Condition:
B-cell Malignancy
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Waldenstrom Macroglobulinemia
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Follicular Lymphoma
Non-Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Waldenstrom Macroglobulinemia
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Docirbrutinib
Description:
oral tablet, twice daily
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion
Other name:
AS-1763
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.
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UC Irvine Health
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Catherine Coombs, MD
Phone:
714-456-8000
Email:
ucstudy@hs.uci.edu
Investigator:
Last name:
Catherine Coombs, MD
Email:
Principal Investigator
Facility:
Name:
Mount Sinai Comprehensive Cancer Center
Address:
City:
Miami Beach
Zip:
33140
Country:
United States
Status:
Recruiting
Contact:
Last name:
Yvonne Enriquez
Phone:
305-674-2625
Email:
yvonne.enriquez@msmc.com
Investigator:
Last name:
Jacqueline Barrientos, MD
Email:
Principal Investigator
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Richard Corona
Phone:
813-745-3465
Email:
richard.corona@moffitt.org
Investigator:
Last name:
Javier Pinilla-Ibarz, MD PhD
Email:
Principal Investigator
Facility:
Name:
Northwestern Memorial Hospital
Address:
City:
Chicago
Zip:
60661
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Cordinator
Phone:
312-695-1301
Email:
cancer@northwestern.edu
Investigator:
Last name:
Shuo Ma, MD PhD
Email:
Principal Investigator
Facility:
Name:
University of Maryland Medical Center - Greenebaum Comprehensive Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nikki M Glynn-Cunningham, MS
Phone:
410-328-7996
Email:
nglynn@umm.edu
Investigator:
Last name:
Seung Tae Lee, MD PhD
Email:
Principal Investigator
Facility:
Name:
University of Massachusetts Memorial Medical Center
Address:
City:
Worcester
Zip:
01655
Country:
United States
Status:
Recruiting
Contact:
Last name:
UMass Cancer Research Office
Phone:
508-856-3216
Email:
cancer.research@umassmed.edu
Investigator:
Last name:
Andrew J Gillis-Smith, MD
Email:
Principal Investigator
Facility:
Name:
Clinical Research Alliance, Inc.
Address:
City:
Westbury
Zip:
11590
Country:
United States
Status:
Recruiting
Contact:
Last name:
James T D'Olimpio, MD FACP FAAHPM
Phone:
646-872-8630
Email:
jdolimpio@researchcra.com
Investigator:
Last name:
James T D'Olimpio, MD FACP FAAHPM
Email:
Principal Investigator
Facility:
Name:
University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nitin Jain, MD
Phone:
713-745-6080
Email:
njain@mdanderson.org
Investigator:
Last name:
Nitin Jain, MD
Email:
Principal Investigator
Facility:
Name:
The Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53266
Country:
United States
Status:
Recruiting
Contact:
Last name:
Medical College of Wisconsin Cancer Center Clinical Trials Office
Phone:
414-805-8900
Email:
cccto@mcw.edu
Investigator:
Last name:
Nirav Shah, MD
Email:
Principal Investigator
Start date:
August 1, 2023
Completion date:
September 2027
Lead sponsor:
Agency:
Carna Biosciences, Inc.
Agency class:
Industry
Source:
Carna Biosciences, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05602363
