Sonrotoclax + Zanubrutinib for Mantle Cell Lymphoma

Recruiting at 139 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: BeiGene

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

Disqualifiers: CNS involvement, Cardiovascular disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL). This study will also look at the safety of sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo.

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 the combination of Sonrotoclax and Zanubrutinib safe for humans?

Zanubrutinib has been studied in patients with mantle cell lymphoma and is generally well-tolerated, with some patients experiencing side effects like high blood pressure, major bleeding, and irregular heartbeats. Although 57% of patients had severe side effects, only 8% stopped treatment, indicating it is fairly well-tolerated. There is no specific safety data available for Sonrotoclax in the provided research. ^{1 2 3 4 5}

What makes the drug combination of Sonrotoclax and Zanubrutinib unique for treating mantle cell lymphoma?

The combination of Sonrotoclax and Zanubrutinib is unique because Zanubrutinib is a next-generation Bruton tyrosine kinase (BTK) inhibitor with high selectivity, which may lead to fewer side effects and better potential for combination with other targeted therapies like Sonrotoclax. This combination could offer a novel approach for patients with relapsed or refractory mantle cell lymphoma, where treatment options are limited. ^{1 2 4 5 6}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Sonrotoclax (Bcl-2 Inhibitor)
• Zanubrutinib (BTK Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy in relapsed/refractory mantle cell lymphoma: a pooled analysis of two clinical trials. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. [2021]

5. United States 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. [2021]

6. England 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. [2023]