Sonrotoclax Combinations for Chronic Lymphocytic Leukemia

Recruiting at 219 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Disqualifiers: Prolymphocytic leukemia, Richter's transformation, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 26 months

630 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatment combinations for people with chronic lymphocytic leukemia or small lymphocytic lymphoma (types of blood cancer) that have returned or resisted treatment. The study compares the effectiveness of sonrotoclax (a new potential drug) with two different drugs—obinutuzumab and rituximab—against the combination of venetoclax and rituximab. Researchers aim to determine which combination is more effective and safer for patients. This trial may suit those previously treated for CLL/SLL who need another treatment option. As a Phase 3 trial, it represents the final step before FDA approval, offering patients early access to potentially effective treatments.

Do I have to stop taking my current medications for the trial?

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

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

Research has shown that sonrotoclax, when used with other treatments, is generally well tolerated. In earlier studies, patients taking sonrotoclax with drugs like zanubrutinib or rituximab experienced manageable side effects. These studies tested doses up to 640 mg and found the treatment safe at these levels.

When combined with rituximab, sonrotoclax demonstrated a good safety profile, even with rapid dose increases. While side effects can occur, they are usually not severe.

For the combination of venetoclax and rituximab, more experience exists because venetoclax is already approved for treating similar conditions. This combination has been extensively studied and is known to be effective and generally safe, though it can cause side effects like low white blood cell counts.

In summary, both treatment options have been shown to be well tolerated. Sonrotoclax combinations appear promising based on past studies, and venetoclax has a well-established safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sonrotoclax because, unlike typical treatments for chronic lymphocytic leukemia (CLL) that often rely on targeting specific proteins like CD20 found on cancer cells, Sonrotoclax works by inhibiting BCL-2, a protein that helps cancer cells survive. This mechanism is different from standard treatments like Rituximab and Obinutuzumab, which primarily act on the cell surface. Additionally, Sonrotoclax, when combined with other drugs like Obinutuzumab or Rituximab, offers a potentially more effective strategy by attacking the cancer cells from different angles. Moreover, using minimal residual disease (MRD) to guide treatment with Sonrotoclax and Obinutuzumab could personalize therapy, ensuring patients receive the most effective treatment duration and intensity.

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

This trial will evaluate different combinations of treatments for chronic lymphocytic leukemia (CLL). Studies have shown that sonrotoclax can help treat CLL by blocking a protein called Bcl-2, which helps cancer cells survive. In this trial, some participants will receive sonrotoclax combined with obinutuzumab. Early research in previously untreated patients showed promising results, with many responding well. Another group in this trial will receive sonrotoclax combined with rituximab, which has been shown to slow or stop cancer cell growth, making it a potentially strong treatment option.

Additionally, another arm of this trial will evaluate venetoclax combined with rituximab, which has already proven effective in treating CLL, with many patients showing significant improvement. This sets a standard for treatment efficacy. Overall, research suggests that these combinations, especially those involving sonrotoclax, offer hope for people with CLL that has returned or hasn't responded to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have had at least one prior treatment. Participants should meet specific CLL criteria, have completed at least two cycles of previous therapy, and be in remission for three years if previously treated with BCL2 inhibitors.

Inclusion Criteria

I have had at least 2 cycles of treatment for my CLL/SLL.

I am able to care for myself and perform daily activities.

My organs are working well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sonrotoclax plus obinutuzumab, sonrotoclax plus rituximab, or venetoclax plus rituximab

Up to approximately 26 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 84 months

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab
• Rituximab
• Sonrotoclax
• Venetoclax

Trial Overview The study compares the effectiveness of sonrotoclax combined with obinutuzumab or rituximab against venetoclax plus rituximab in treating CLL/SLL. It aims to determine which combination leads to longer progression-free survival while also evaluating the safety of these treatments.

How Is the Trial Designed?

Group I: Arm C: Sonrotoclax plus Obinutuzumab (MRD) Experimental Treatment 2 Interventions

Sonrotoclax and obinutuzumab will be administered in combination with treatment guided by evaluation of minimal residual disease (MRD).

Group II: Arm B: Sonrotoclax plus Rituximab Experimental Treatment 2 Interventions

Sonrotoclax and rituximab will be administered in combination.

Group III: Arm A: Sonrotoclax plus Obinutuzumab Experimental Treatment 2 Interventions

Sonrotoclax and obinutuzumab will be administered in combination.

Group IV: Arm D: Venetoclax plus Rituximab Active Control 2 Interventions

Venetoclax and rituximab will be administered in combination.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

German CLL Study Group

Collaborator

Trials

49

Recruited

21,400+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06849713

Zanubrutinib, Obinutuzumab, and Sonrotoclax in ... This is a multicenter phase II study evaluating zanubrutinib, obinutuzumab, and sonrotoclax in previously untreated patients with CLL or SLL.

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 Blood. 2024;144(18):1924-1935. • CLL/SLL remains incurable as many treated patients experience relapse,1 necessitating further.

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 progression- ...

4. 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: Data from an Ongoing ...

5. 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 ...

6. 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 ...