Sonrotoclax + Zanubrutinib for Chronic Lymphocytic Leukemia

Not currently recruiting at 48 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BeiGene

Disqualifiers: Cardiovascular, Pulmonary, Malignancy, Infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 15 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, sonrotoclax and zanubrutinib, for treating chronic lymphocytic leukemia (CLL), a type of blood cancer. Researchers aim to determine if adding sonrotoclax enhances the treatment's effectiveness. Participants will receive either the combination therapy or zanubrutinib alone, allowing for a comparison of results. This trial suits individuals with CLL who have not received prior treatment and currently require it. Participants should have a stable health condition and be able to adhere to the study guidelines.

As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that the combination of sonrotoclax and zanubrutinib is generally safe for people with chronic lymphocytic leukemia (CLL). In earlier studies, most patients taking this combination did not experience serious side effects, indicating a good safety profile.

Some minor side effects, such as tiredness and mild nausea, were observed, but these were uncommon and manageable. Importantly, no unexpected safety issues emerged.

Zanubrutinib's approval for other conditions further supports its safety. Overall, early studies suggest that the combination of sonrotoclax and zanubrutinib holds promise in terms of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sonrotoclax and Zanubrutinib for treating Chronic Lymphocytic Leukemia (CLL) because it offers a fresh approach compared to current therapies. Unlike standard treatments, which often focus on single pathways, this combination targets multiple cancer growth mechanisms. Sonrotoclax is a novel BCL-2 inhibitor, which works by prompting cancer cells to self-destruct, while Zanubrutinib is a BTK inhibitor that disrupts signals needed for cancer cell survival. This dual-action strategy could potentially increase treatment efficacy and overcome resistance seen with current options.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research shows that the combination of sonrotoclax and zanubrutinib holds promise for treating chronic lymphocytic leukemia (CLL). In this trial, participants in Arm A will receive this combination therapy. Studies have found that this treatment can significantly reduce cancer cells, with high rates of minimal residual disease (MRD) clearance. All patients in previous studies responded to the combination treatment, achieving a 100% overall response rate. Additionally, the treatment is generally well-tolerated, with patients usually not experiencing severe side effects. These findings suggest that this combination could be a strong option for those with untreated CLL. Meanwhile, participants in Arm B will receive zanubrutinib monotherapy, which researchers will evaluate for its effectiveness and safety as a standalone treatment. ^{1 3 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

This trial is for adults over 18 with untreated Chronic Lymphocytic Leukemia (CLL) who need treatment. Participants should be relatively healthy, able to perform daily activities with ease or some effort, and have measurable disease via scans. They must have good marrow, liver, and kidney function, agree to birth control if applicable, understand the study protocol and consent to participate.

Inclusion Criteria

I have signed the consent form and can follow the study's requirements.

My kidney function is normal.

My cancer can be measured with a scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sonrotoclax combined with zanubrutinib or zanubrutinib monotherapy. Combination therapy is administered for a fixed duration of 15 cycles.

15 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and response rates.

Up to 66 months

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival.

Up to 66 months

What Are the Treatments Tested in This Trial?

Interventions

• Sonrotoclax
• Zanubrutinib

Trial Overview

The study is testing the effectiveness of combining Sonrotoclax with Zanubrutinib versus using Zanubrutinib alone in treating CLL. The goal is to see if adding Sonrotoclax improves outcomes for patients who haven't been treated before.

How Is the Trial Designed?

Group I: Arm A: Combination Therapy: Sonrotoclax + Zanubrutinib Experimental Treatment 2 Interventions

Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles.

Group II: Arm B: Monotherapy: Zanubrutinib Active Control 1 Intervention

Participants will receive zanubrutinib monotherapy daily until disease progression or unacceptable toxicity, whichever occurs first.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

BeOne Medicines

Lead Sponsor

Published Research Related to This Trial

In a study of 23 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), BTK inhibitors (ibrutinib and zanubrutinib) were found to provide durable disease control after patients progressed on venetoclax, with a median progression-free survival of 34 months.

Patients who had a prior remission duration of 24 months or longer and those who achieved complete remission on venetoclax experienced significantly longer progression-free survival after starting BTK inhibitors, highlighting the importance of previous treatment response in predicting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax. Lin, VS., Lew, TE., Handunnetti, SM., et al.[2021]

In a phase 3 study involving 590 patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to bendamustine-rituximab, with a hazard ratio of 0.42, indicating a strong efficacy advantage.

Zanubrutinib demonstrated an acceptable safety profile, with fewer severe adverse events like neutropenia compared to bendamustine-rituximab, suggesting it could be a promising new treatment option for patients with CLL and SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Tam, CS., Brown, JR., Kahl, BS., et al.[2023]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, showed a high overall response rate of 94.5% in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma carrying the del(17p) mutation, indicating its efficacy in a challenging patient population.

The treatment was well tolerated, with an estimated 18-month progression-free survival rate of 88.6% and an overall survival rate of 95.1%, although some patients experienced adverse events, including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Tam, CS., Robak, T., Ghia, P., et al.[2021]

Zanubrutinib, a selective BTK inhibitor, was well-tolerated in a phase 1 study with 144 patients, showing no dose-limiting toxicities and achieving over 95% BTK occupancy in blood cells at all tested doses.

In patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), zanubrutinib demonstrated a remarkable overall response rate of 96.2% and a 100% estimated progression-free survival at 12 months, indicating strong efficacy with low major toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Tam, CS., Trotman, J., Opat, S., et al.[2021]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, was found to be generally well tolerated when combined with obinutuzumab in a phase 1 study involving 81 patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

The combination therapy showed high efficacy, achieving a 100% overall response rate in treatment-naïve CLL patients and a 92% response rate in relapsed/refractory CLL patients, with a 72% response rate in relapsed/refractory FL patients over a median follow-up of 20 to 29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Tam, CS., Quach, H., Nicol, A., et al.[2021]

In a murine model of chronic lymphocytic leukemia (CLL), the combination of ibrutinib and venetoclax showed greater efficacy than either drug alone, leading to deeper responses and longer-lasting effects due to reduced cell proliferation and increased apoptosis.

The combination treatment also positively altered the T-cell compartment, increasing naive T-cells and decreasing effector memory T-cells, although resistance to treatment eventually developed, linked to downregulation of BIM expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined ibrutinib and venetoclax treatment vs single agents in the TCL1 mouse model of chronic lymphocytic leukemia. Kater, AP., Slinger, E., Cretenet, G., et al.[2022]

In a phase 2 study involving 37 patients with chronic lymphocytic leukaemia, the combination therapy of acalabrutinib, venetoclax, and obinutuzumab achieved a complete remission with undetectable minimal residual disease (MRD) in 38% of participants by cycle 16, indicating promising efficacy.

The treatment was generally well tolerated, with the most common serious adverse event being neutropenia, affecting 43% of patients, and no deaths reported during the study, suggesting a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Davids, MS., Lampson, BL., Tyekucheva, S., et al.[2021]

Zanubrutinib (zanu) has been shown to significantly improve progression-free survival compared to bendamustine-rituximab in treatment-naive patients with chronic lymphocytic leukemia (CLL), indicating its efficacy as a first-line treatment option.

In a direct comparison with ibrutinib, zanu demonstrated a better safety profile and enhanced clinical efficacy, leading to its approval by the FDA and EMA as a preferred treatment for CLL/SLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option. Molica, S., Tam, C., Allsup, D., et al.[2023]

In the phase 3 SEQUOIA trial involving adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to the standard treatment of bendamustine plus rituximab (BR).

Patients treated with zanubrutinib reported better health-related quality-of-life outcomes at 12 and 24 weeks, including improvements in global health status, physical functioning, and reduced symptoms of diarrhea, fatigue, and nausea/vomiting compared to those receiving BR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. Ghia, P., Barnes, G., Yang, K., et al.[2023]

Citations

1.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/1012/531224/Sonrotoclax-and-Zanubrutinib-as-Frontline

Sonrotoclax and Zanubrutinib as Frontline Treatment for CLL ...

Sonrotoclax and Zanubrutinib as frontline treatment for CLL demonstrates high MRD clearance rates with good tolerability.

2.

haematologica.org

haematologica.org/article/view/12854

SONROTOCLAX AND ZANUBRUTINIB AS FRONTLINE ...

CONCLUSIONS: Sonrotoclax + zanubrutinib was well tolerated in patients with TN-CLL/SLL. Substantial efficacy was observed, with 100% ORR in ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06073821

Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib ...

It is hypothesized that sonrotoclax plus zanubrutinib may be better than venetoclax plus obinutuzumab in treating CLL. The main purpose of this study is to ...

4.

cancernetwork.com

cancernetwork.com/view/sonrotoclax-zanubrutinib-combo-elicits-deep-responses-for-untreated-cll-sll

Sonrotoclax/Zanubrutinib Combo Elicits Deep Responses ...

For patients with CLL and SLL, sonrotoclax with zanubrutinib yielded high rates of overall response in the phase 1/1b BGB-11417-101 study.

5.

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

... efficacy data, including preliminary results from time-limited therapy, are ... presented for patients with R/R CLL/SLL treated with sonrotoclax + ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06637501

NCT06637501 | A Study to Investigate Sonrotoclax ...

This study will test how effective and safe Sonrotoclax plus Zanubrutinib treatment compared with Zanubrutinib alone in participants with previously untreated ...

7.

conference-correspondent.com

conference-correspondent.com/highlights/ash/ash-2023-cll/phase-1-2-study-data-of-combination-sonrotoclax-bgb-11417-plus-zanubrutinib-in-treatment-naive-cll-sll

Phase 1/2 Study Data of Combination Sonrotoclax (BGB- ...

Data from an ongoing, first-in-human phase 1/2 study suggests that combination sonrotoclax (160 mg and 320 mg) plus zanubrutinib therapy was well tolerated ...