This is a single-arm, open-label study of sonrotoclax plus zanubrutinib with MRD-driven treatment duration in patients with previously untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). The primary goal of this study is to evaluate the efficacy of MRD-guided zanubrutinib plus sonrotoclax for first-line CLL/SLL treatment.
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are often considered different variations of the same disease due to their many similarities. There is an urgent need for new treatments to improve patients' quality of life, prolong survival, and manage disease-related symptoms. There are several different methods for treating front-line therapy, including Chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitors (BTKis), and BCL-2 inhibitors (BCL2is). Continuous treatment with BTK inhibitors is necessary for the treatment of CLL or SLL. However, younger patients may need to limit their therapeutic duration. The combination of BTK inhibitors and BCL-2 inhibitors is believed to be an optimizing regimen that provides a limited duration of therapy. The main aim of this study is to assess whether MRD-guided zanubrutinib, in combination with sonrotoclax, can be an effective first-line treatment option for adult patients with treatment-naïve CLL or SLL. The goal is to achieve long-lasting and more profound responses, which could allow for the possibility of discontinuing treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Participants receive zanubrutinib orally 160mg bid from start of Cycle 1, and in combination with sonrotoclax (SZ) from Cycle 4 onwards at increasing doses until 320mg daily target dose is reached and continuing for at least 12 cycles (each cycle is 28 days). Participants with uMRD and PR/CR by the end of Cycle 15 will stop SZ treatment, others will continue to receive SZ for another 12 cycles and stop SZ if uMRD and PR/CR. Participants will receive sonrotoclax up to 2 years, and receive zanubrutinib for those with MRD-positive by then.
Participants receive zanubrutinib orally 160mg bid from start of Cycle 1,Participants with uMRD and PR/CR by the end of Cycle 15 will stop SZ treatment, others will continue to receive SZ for another 12 cycles and stop SZ if uMRD and PR/CR. Participants will receive sonrotoclax up to 2 years, and receive zanubrutinib for those with MRD-positive by then.
4-Year Progressive Free Survival (PFS) Rate
PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by investigators
Time frame: 4 years after enrollment
Rate of peripheral blood (PB) and Bone marrow (BM) undetectable minimal residual disease (uMRD)
Rate of PB and BM uMRD is defined as proportion of participants achieving remission based on flow cytometry (FCM) result of \< 1 CLL cell per 100,000 leukocytes (\< 10 \^-4 ), after completion of 12 and 24 cycles of sonrotoclax treatment.
Time frame: At screening, the end of Cycle 14 and Cycle 26 (each cycle is 28 days)
Complete Response Rate (CRR; Complete Response/Complete Response with Incomplete Blood Count Recovery [CR/CRi]) Rate
CR/CRi rate is defined as the percentage of participants achieving a response of complete response (CR), CR with incomplete blood count recovery (CRi) per 2018 IWCLL criteria, as determined by investigators
Time frame: Up to 4 years
Overall Response Rate (ORR)
ORR is defined as the percentage of participants achieving a response of complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PRL) evaluated under the 2018 IWCLL criteria, as determined byinvestigators
Time frame: Up to 4 years
Duration of Response (DOR)
DOR was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2018 IWCLL response criteria in CLL or a response (PR or better) based on 2014 Lugano response criteria and defined as the interval between the date of initial documentation of a response mentioned above until disease progression (PD) or death from any cause, whichever occurred first
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Time frame: Up to 4 years
Progression Free Survival (PFS)
PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by investigators
Time frame: Up to 4 years
Overall Survival (OS)
OS is defined as time from the date of enrollment to the date of death because of any cause
Time frame: Up to 4 years
Time to Next Therapy (TTNT)
Time to next CLL or SLL therapy is defined as the time from the first administration of study drugs to the first administration of the next CLL/SLL treatment, as determined by investigators
Time frame: Up to 4 years
Overall survival rate
Number, time frame and seriousness of participants with Treatment-Emergent Adverse Events (NCI-TEAE v5.0)
Time frame: Up to 4 years