Sonrotoclax + Zanubrutinib for Blood Cancers
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: BeiGene
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.
What makes the drug Sonrotoclax + Zanubrutinib unique for blood cancers?
Sonrotoclax + Zanubrutinib is unique because it combines two drugs that target different pathways in cancer cells, potentially improving effectiveness and reducing resistance compared to single-drug treatments. This combination may offer synchronized and enhanced uptake in cancer cells, leading to longer-lasting effects and potentially better outcomes for patients with blood cancers.
13458Is the combination of Sonrotoclax and Zanubrutinib safe for humans?
The combination of venetoclax (similar to Sonrotoclax) and zanubrutinib has shown improved safety and tolerability compared to traditional chemotherapies in leukemia treatments. However, higher doses can cause dose-limiting toxicities, so careful dosing is important to avoid side effects.
12578Do I need to stop my current medications to join the trial?
The trial information does not specify whether you need to stop taking your current medications. However, since prior systemic treatment for CLL is an exclusion criterion, it might be necessary to stop certain treatments. Please consult with the trial coordinators for specific guidance.
What data supports the effectiveness of the drug Sonrotoclax + Zanubrutinib for blood cancers?
Research shows that combining zanubrutinib with other drugs like venetoclax can lead to high rates of undetectable cancer cells in certain blood cancers, suggesting potential effectiveness. Additionally, a novel formulation combining venetoclax and zanubrutinib has shown enhanced uptake and longer-lasting effects in leukemia cells, indicating promise for treating blood cancers.
12456Eligibility Criteria
This trial is for people with certain blood cancers like lymphoma or chronic lymphocytic leukemia. Participants should be relatively stable (ECOG ≤ 2), have good organ function, and not have had recent blood transfusions. They must use effective birth control and can't donate eggs during the study. A confirmed diagnosis of CLL requiring treatment and at least one measurable lesion are needed.Inclusion Criteria
I have at least one tumor that can be measured on a scan and no history of specific leukemia types.
I have been diagnosed with CLL and need treatment.
My physical health status has been stable.
Exclusion Criteria
I have received treatment for my CLL before.
I have an untreated autoimmune blood disorder.
Participant Groups
The study tests new dosing schedules for a drug called Sonrotoclax in patients with blood cancers, alongside another drug named Zanubrutinib. The goal is to find out how safe these novel dose ramp-up schedules are when starting Sonrotoclax treatment.
2Treatment groups
Experimental Treatment
Group I: Part 2: Schedule ExpansionExperimental Treatment2 Interventions
Participants will receive zanubrutinib monotherapy with fixed duration, followed by combination sonrotoclax with zanubrutinib at ramp-up schedules as determined in Part 1.
Group II: Part 1: Schedule CalibrationExperimental Treatment2 Interventions
Participants will receive zanubrutinib monotherapy with fixed duration, followed by combination sonrotoclax with zanubrutinib at protocol-defined ramp-up schedules until target daily dose will be reached.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Fort Wayne Medical Oncology and HematologyFort Wayne, IN
The University of Kansas Cancer CenterWestwood, KS
Dana Farber Cancer InstituteBoston, MA
Washington UniversitySaint Louis, MO
More Trial Locations
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Who is running the clinical trial?
BeiGeneLead Sponsor
References
Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial. [2022]We hypothesised that combining zanubrutinib with obinutuzumab and venetoclax (BOVen) as an initial therapy for chronic lymphocytic leukaemia and small lymphocytic lymphoma would lead to high rates of undetectable minimal residual disease (MRD), and we explored MRD as a biomarker for directing treatment duration.
Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. [2023]To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia.
A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). [2022]Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML.
TP53 or Not TP53: That Is the Question. [2023]Azacitidine and venetoclax are a standard first-line regimen for patients with newly diagnosed unfit acute myeloid leukemia (AML). In a pooled subset analysis, TP53-mutated AML with poor-risk cytogenetics does not appear to benefit from the addition of venetoclax to azacitidine. This has clinical implications as these patients should be preferentially treated with alternative regimens. See related article by Pollyea et al., p. 5272.
Design and Characterization of a Novel Venetoclax-Zanubrutinib Nano-Combination for Enhancing Leukemic Cell Uptake and Long-Acting Plasma Exposure. [2023]Leukemia remains incurable partly due to difficulties in reaching and maintaining therapeutic drug concentrations in the target tissues and cells. Next-generation drugs targeted to multiple cell checkpoints, including the orally active venetoclax (Bcl-2 target) and zanubrutinib (BTK target), are effective and have improved safety and tolerability compared to conventional, nontargeted chemotherapies. However, dosing with a single agent frequently leads to drug resistance; asynchronous coverage due to the peak-and-trough time-course of two or more oral drugs has prevented drug combinations from simultaneously knocking out the respective drugs' targets for sustained leukemia suppression. Higher doses of the drugs may potentially overcome asynchronous drug exposure in leukemic cells by saturating target occupancy, but higher doses often cause dose-limiting toxicities. To synchronize multiple drug target knockout, we have developed and characterized a drug combination nanoparticle (DcNP), which enables the transformation of two short-acting, orally active leukemic drugs, venetoclax and zanubrutinib, into long-acting nanoformulations (VZ-DCNPs). VZ-DCNPs exhibit synchronized and enhanced cell uptake and plasma exposure of both venetoclax and zanubrutinib. Both drugs are stabilized by lipid excipients to produce the VZ-DcNP nanoparticulate (d ~ 40 nm) product in suspension. The VZ-DcNP formulation has enhanced uptake of the two drugs (VZ) in immortalized leukemic cells (HL-60), threefold over that of its free drug counterpart. Additionally, drug-target selectivity of VZ was noted with MOLT-4 and K562 cells that overexpress each target. When given subcutaneously to mice, the half-lives of venetoclax and zanubrutinib were extended by approximately 43- and 5-fold, respectively, compared to an equivalent free VZ. Collectively, these data suggest that VZ in VZ-DcNP warrant consideration for preclinical and clinical development as a synchronized and long-acting drug-combination for the treatment of leukemia.
The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. [2023]The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
Unmet clinical needs in the use of zanubrutinib in malignant lymphomas (Waldenström macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma): A consensus-based position paper from an ad hoc expert panel. [2023]Zanubrutinib has been approved for the treatment of patients with different lymphoproliferative disorders, and now represents a major breakthrough in the treatment of patients resistant or relapsing after the recommended therapies. Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of the drug in approved indications is challenging, and questions are emerging on its use in earlier stages of the disorders. This article presents the results of group discussion among an ad hoc constituted panel of experts aimed at identifying and addressing unmet clinical needs (UCNs) in the use of zanubrutinib in the lymphomas which have received the approval of use, specifically Waldenström macroglubulinemia, marginal zone lymphoma and mantle cell lymphoma. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. The panel produced recommendations and proposals for new studies for the management of the identified UCNs. These recommendations are intended for use not only by expert centers but above all by not experienced hematologists as well as general practitioners.
[Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia]. [2023]To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.