Sonrotoclax + Zanubrutinib for Blood Cancers

Recruiting at 25 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

Disqualifiers: Active HBV, HCV, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety of combining two treatments, sonrotoclax (a new potential drug) and zanubrutinib, for people with certain blood cancers. It will explore different schedules for administering these medications to find the safest approach. Good candidates for this trial include those with chronic lymphocytic leukemia (CLL) who require treatment due to specific disease features and have at least one measurable lesion from scans.

As a Phase 1 trial, participants will be among the first to receive this new treatment combination, aiding researchers in understanding its effects in people.

Do 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of sonrotoclax and zanubrutinib is generally well-tolerated by patients with certain blood cancers. Earlier studies revealed that most patients could handle this combination's safety profile without severe side effects. Specifically, patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) found the treatment manageable at all tested doses.

Zanubrutinib, a component of this treatment, is known for causing fewer serious side effects, particularly those affecting the heart, compared to similar drugs.

For those considering joining a trial, these findings help set expectations about safety. However, each person may react differently, and ongoing studies aim to determine the best dosages for optimal results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for blood cancers, which often include chemotherapy and immunotherapy, sonrotoclax and zanubrutinib offer a novel approach by targeting specific proteins involved in cancer cell survival and growth. Sonrotoclax works by inhibiting a protein called BCL-2, which helps cancer cells avoid death, while zanubrutinib blocks BTK, a key player in cancer cell signaling. Researchers are excited about this combination because it simultaneously disrupts two critical pathways that cancer cells rely on, potentially leading to more effective and durable responses in patients. This dual-targeted strategy could offer a more precise and potent attack against blood cancers, reducing the likelihood of resistance and improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for blood cancers?

Research has shown that the combination of sonrotoclax and zanubrutinib holds promise for treating blood cancers such as chronic lymphocytic leukemia (CLL). In this trial, participants will first receive zanubrutinib monotherapy, followed by the combination with sonrotoclax. Sonrotoclax blocks a protein called Bcl-2, which aids cancer cell growth. This action can slow or halt cancer growth and promote cell death. Studies have found that this combination is effective and has fewer side effects compared to older treatments like ibrutinib and venetoclax. Early results also suggest high overall response rates (ORR) in patients, indicating that many experience tumor shrinkage or disappearance. ^{2 3 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

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.

My organs are working well and I haven't had recent blood treatments.

I have been diagnosed with CLL and need treatment.

Exclusion Criteria

Positive HIV serology (HIVAb) status unless certain conditions are met

Participants unable to comply with the requirements of the protocol

Serologic status reflecting active viral HBV or HCV infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Schedule Calibration

Participants receive zanubrutinib monotherapy followed by combination sonrotoclax with zanubrutinib at protocol-defined ramp-up schedules until target daily dose is reached

Approximately 4 months

Schedule Expansion

Participants receive zanubrutinib monotherapy followed by combination sonrotoclax with zanubrutinib at ramp-up schedules as determined in Part 1

Approximately 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sonrotoclax

Trial Overview

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.

How Is the Trial Designed?

Group I: Part 2: Schedule Expansion Experimental Treatment 2 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 Calibration Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a study comparing treatment regimens for relapsed/refractory acute myeloid leukemia (R/R AML), the venetoclax (VEN) combination therapy showed a comparable overall response rate (59.3%) to intensive chemotherapy (IC) (44.0%), suggesting it is an effective alternative for patients who have failed previous treatments.

Patients receiving the VEN combination had a significantly higher percentage of successful stem cell transplants at blast clearance (86.5% vs. 62.3% for IC), indicating better disease control and potentially lower treatment-related mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). Park, S., Kwag, D., Kim, TY., et al.[2022]

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a phase 2 trial involving 39 patients with treatment-naive chronic lymphocytic leukaemia or small lymphocytic lymphoma, the combination therapy of zanubrutinib, obinutuzumab, and venetoclax (BOVen) achieved an impressive 89% rate of undetectable minimal residual disease (MRD) in both blood and bone marrow after a median treatment duration of 10 months.

The BOVen regimen was well tolerated, with the most common side effects being thrombocytopenia and neutropenia, and it supports the idea of using MRD as a biomarker to guide treatment duration, potentially allowing for earlier therapy discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Soumerai, JD., Mato, AR., Dogan, A., et al.[2022]

In a study of 79 patients with acute myeloid leukemia (AML), the venetoclax-based regimen achieved a high overall response rate of 64.6%, with a significantly higher complete remission rate in newly diagnosed unfit AML patients compared to those with relapsed/refractory AML (60.5% vs 27.8%).

The median overall survival for unfit AML patients was notably longer at 14.1 months, especially for those with NPM1 or IDH1/2 mutations, while the regimen was found to be tolerable despite a high incidence of adverse effects, primarily infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia]. Kong, FC., Qi, L., Huang, WF., et al.[2023]

In a pooled analysis of treatment-naïve patients with FLT3-mutant acute myeloid leukemia, the combination of venetoclax and azacitidine resulted in a significantly higher composite complete remission rate (67%) compared to azacitidine alone (36%), with a median overall survival of 12.5 months versus 8.6 months.

The treatment was found to be safe, with no unexpected toxicities reported, indicating that venetoclax + azacitidine is a promising option for older patients or those with comorbidities who are ineligible for intensive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia. Konopleva, M., Thirman, MJ., Pratz, KW., et al.[2023]

Zanubrutinib has been approved for treating various lymphoproliferative disorders, providing a significant option for patients who have not responded to standard therapies.

A panel of experts identified unmet clinical needs in the use of zanubrutinib for specific lymphomas, such as Waldenström macroglobulinemia, and made recommendations for future studies to optimize its use, especially for less experienced healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Zinzani, PL., Mauro, FR., Tedeschi, A., et al.[2023]

The development of a drug combination nanoparticle (DcNP) formulation, VZ-DcNP, allows for synchronized delivery of venetoclax and zanubrutinib, enhancing their uptake in leukemic cells by threefold compared to free drugs.

VZ-DcNP significantly extends the half-lives of venetoclax and zanubrutinib in mice, by approximately 43-fold and 5-fold respectively, suggesting improved therapeutic potential for sustained leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Characterization of a Novel Venetoclax-Zanubrutinib Nano-Combination for Enhancing Leukemic Cell Uptake and Long-Acting Plasma Exposure. Griffin, J., Wu, Y., Mu, Q., et al.[2023]

The combination of venetoclax (Ven) and azacitidine (AZA) shows a high efficacy in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), with an overall complete response rate of 57.9% across 19 studies involving 1615 patients.

This treatment is particularly effective for newly diagnosed AML patients, achieving a complete response rate of 67.5%, although it is less effective for those with relapsed or refractory AML, which had a response rate of only 30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. Du, Y., Li, C., Yan, J.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06637501

NCT06637501 | A Study to Investigate Sonrotoclax ...

When Sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with CLL disease.

2.

beonemedinfo.com

beonemedinfo.com/CongressDocuments/Cheah_BGB-11417-101_SZ_RR_CLL_EHA_Presentation_2025.pdf

Updated Results From the Phase 1 Study of Sonrotoclax

• Sonrotoclax + zanubrutinib combination treatment had a tolerable safety profile in patients with. R/R CLL/SLL at all dose levels tested up ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7087

CELESTIAL-TNCLL: An ongoing, open-label, multiregional ...

In a phase 1 study in patients with TN CLL treated with sonrotoclax + zanubrutinib, efficacy data was promising with ORR and 1-year ...

4.

healthtree.org

healthtree.org/cll/community/articles/ash-24-sonrotoclax-zanubrutinib-first-cll-therapy

Sonrotoclax + Zanubrutinib: First CLL Treatment

This duo has shown improved effectiveness and fewer side effects compared to its first-generation counterparts, ibrutinib and venetoclax. A ...

5.

cancer.gov

cancer.gov/research/participate/clinical-trials/intervention/sonrotoclax?pn=1

Clinical Trials Using Sonrotoclax - NCI

A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers. Status: Active.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06697184

NCT06697184 | A Study to Investigate the Safety of Novel ...

The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.

7.

cllsociety.org

cllsociety.org/2025/01/sonrotoclax-and-zanubrutinib-as-a-frontline-cll-treatment/

Sonrotoclax and Zanubrutinib as a Frontline CLL Treatment

The combination of sonrotoclax and zanubrutinib was well-tolerated and produced high rates of undetectable disease in patients with treatment-naïve CLL.