Sonrotoclax + Zanubrutinib for Mantle Cell Lymphoma

Recruiting at 210 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Must not be taking: BCL-2 inhibitors, BTK inhibitors

Disqualifiers: CNS involvement, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 66 months

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with mantle cell lymphoma (MCL) that has returned or not responded to treatment. It compares the effectiveness of two drugs, sonrotoclax (a potential new drug) and zanubrutinib, against zanubrutinib with a placebo. The study evaluates both the treatment's effectiveness and its safety. Eligible participants have MCL, have tried other treatments, and still need help managing their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if 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?

Previous studies have shown that the combination of sonrotoclax and zanubrutinib is safe for patients with conditions like mantle cell lymphoma that have returned or are resistant to treatment. Research indicates that most patients tolerate this treatment well. No severe side effects prevented patients from continuing the treatment. While some side effects occurred, they were manageable. The data suggest that patients tolerate this treatment combination well, with safety closely monitored throughout the studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mantle cell lymphoma because they offer a new approach that differs from current options. Sonrotoclax is unique in that it targets BCL-2 proteins, which are often overexpressed in cancer cells, leading to their survival. Zanubrutinib, on the other hand, is a next-generation BTK inhibitor that specifically targets and blocks the enzyme responsible for cancer cell growth. Together, these treatments aim to more effectively disrupt cancer cell survival and proliferation compared to existing therapies, potentially offering a more powerful one-two punch against the disease.

What evidence suggests that sonrotoclax plus zanubrutinib could be an effective treatment for mantle cell lymphoma?

Research has shown that combining sonrotoclax and zanubrutinib holds promise for treating relapsed or hard-to-treat mantle cell lymphoma (MCL). In this trial, participants in Arm A will receive sonrotoclax plus zanubrutinib. Studies found that this combination led to a 79% overall response rate (ORR) and a 66% complete response (CR) rate, indicating many patients experienced a reduction or disappearance of their cancer. Sonrotoclax blocks a protein called Bcl-2, which stops cancer cells from growing and encourages them to die. This treatment is generally safe, with most patients experiencing manageable side effects. Overall, these findings suggest this treatment could be effective for those with difficult cases of MCL. ^{2 3 4 5 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 mantle cell lymphoma (MCL) who have tried 1-5 treatments including immunotherapy or chemoimmunotherapy and whose disease has come back or didn't respond. They must have a measurable size of cancer, be able to do some daily activities on their own, and have organs that are working well.

Inclusion Criteria

My organs are working well.

My diagnosis of mantle cell lymphoma is confirmed by the latest WHO or ICC standards.

I've had 1-5 treatments including an anti-CD20 drug and my disease didn't respond or has come back.

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 zanubrutinib or placebo plus zanubrutinib

Approximately 66 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 26 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Sonrotoclax
• Zanubrutinib

Trial Overview The study compares the effectiveness and safety of two combinations: Sonrotoclax plus Zanubrutinib versus Zanubrutinib with a placebo in treating MCL that has returned after treatment or hasn't responded to previous treatments.

How Is the Trial Designed?

Group I: Arm A: sonrotoclax plus zanubrutinib Experimental Treatment 2 Interventions

Sonrotoclax and zanubrutinib will be administered in combination.

Group II: Arm B: placebo plus zanubrutinib Placebo Group 2 Interventions

Placebo and zanubrutinib will be administered in combination.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Zanubrutinib monotherapy demonstrated a high overall response rate of 84.8% and a complete response rate of 62.5% in 112 patients with relapsed/refractory mantle cell lymphoma, with a median follow-up of approximately 25 months.

The treatment was well-tolerated, with only 12.5% of patients experiencing treatment discontinuation due to adverse events, and serious side effects like hypertension and major hemorrhage occurring at relatively low rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy in relapsed/refractory mantle cell lymphoma: a pooled analysis of two clinical trials. Zhou, K., Zou, D., Zhou, J., et al.[2021]

Zanubrutinib, a second-generation BTK inhibitor, has shown an impressive overall response rate of 84% in treating relapsed/refractory mantle cell lymphoma (MCL) based on data from 118 patients in two clinical trials, with a duration of response lasting 14-18 months.

Despite 57% of patients experiencing significant side effects, only 8% discontinued treatment, indicating that zanubrutinib is generally well tolerated and may offer advantages over first-generation BTK inhibitors like ibrutinib due to its higher selectivity and potential for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. Weaver, AN., Jimeno, A.[2020]

The combination of venetoclax (VEN) and ibrutinib (IBR) showed a high overall response rate of 93.8% at the optimal dosing of VEN 200 mg and IBR 420 mg in treating relapsed mantle cell lymphoma (MCL) among 35 participants.

The study found that higher doses of VEN and IBR did not improve efficacy and were associated with increased toxicity, highlighting the importance of dose optimization in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. Portell, CA., Wages, NA., Kahl, BS., et al.[2022]

In a phase II study involving 86 patients with relapsed mantle-cell lymphoma, zanubrutinib demonstrated a high overall response rate of 84%, with 68.6% achieving a complete response after a median follow-up of 18.4 months.

Zanubrutinib was generally well tolerated, with most adverse events being manageable; serious side effects like major bleeding were rare, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Song, Y., Zhou, K., Zou, D., et al.[2021]

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., 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]

Citations

1. onclive.com onclive.com/view/sonrotoclax-plus-zanubrutinib-generates-durable-responses-in-r-r-mantle-cell-lymphoma

Sonrotoclax Plus Zanubrutinib Generates Durable ... Sonrotoclax combined with zanubrutinib achieved a 79% ORR and 66% CR rate in patients with relapsed/refractory MCL. No dose-limiting toxicities ...

2. ajmc.com ajmc.com/view/positive-topline-results-seen-for-sonrotoclax-in-r-r-mantle-cell-lymphoma

Positive Topline Results Seen for Sonrotoclax in R/R ... Sonrotoclax showed significant efficacy in relapsed or refractory mantle cell lymphoma, achieving a high overall response rate and manageable ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06839053

Study Details | NCT06839053 | Sonrotoclax, Rituximab ... When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. Giving an increased dose of sonrotoclax over a shorter period ...

4. haematologica.org haematologica.org/article/view/12767

DP003 | COMBINATION TREATMENT WITH NOVEL BCL2 ... RESULTS: As of 6 Dec 2024, 49 pts with R/R MCL were enrolled and treated (sonro 80 mg, n=6; 160 mg, n=13; 320 mg, n=25; 640 mg, n=5): 7 were in ...

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

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06742996

NCT06742996 | A Study to Investigate the Efficacy and ... The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with ...