ActiveCancerNIHR-supported projectDigestion, Kidneys & Other Organs
A Phase 3 Randomized Double-Blind Multicenter Study of Sonrotoclax PlusZanubrutinib Versus Placebo Plus Zanubrutinib in Patients WithRelapsed/Refractory Mantle Cell Lymphoma
Recipient organisationNIHR University College London Hospitals Biomedical Research Centre
NIHR supportRecorded as supported by this research centre
PeriodMar 2025 — Jun 2032
In plain English
AI plain-English summary
A clinical trial is testing whether combining two targeted cancer drugs—sonrotoclax and zanubrutinib—can shrink tumours and extend survival in 300 patients with mantle cell lymphoma that has stopped responding to previous treatment. Mantle cell lymphoma is an aggressive blood cancer that often relapses after standard therapy. Current treatments that block a single cancer-driving protein, such as zanubrutinib alone, eventually stop working as tumours evolve resistance. This trial addresses that gap by simultaneously disabling two different survival mechanisms: zanubrutinib blocks the BTK protein that fuels cancer cell growth, while sonrotoclax blocks the BCL2 protein that prevents cancer cells from dying. The hypothesis is that this dual attack will kill more lymphoma cells than zanubrutinib alone. If the combination proves superior, it could become a new standard of care for relapsed/refractory mantle cell lymphoma—offering patients a chemotherapy-free, oral treatment option that delays disease progression and reduces the need for more toxic salvage therapies. The trial is double-blind and randomised, with results expected after roughly five years of follow-up.
View original technical description
The purpose of this study is to test if sonrotoclax in combination with zanubrutinib is safe and works better in treating adult patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) comparing it with when zanubrutinib is given in combination with sonrotoclax-matched placebo (the placebo is an inactive dummy drug that looks like the sonrotoclax medication).Zanubrutinib works by blocking a protein called Bruton tyrosine kinase (BTK). BTK helps cancer cells to grow. By blocking BTK, zanubrutinib interferes with the signals needed for the cancer cells to multiply and survive. This helps slow down or stop the growth of cancer cells and can reduce the number of cancer cells. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (BCL2). This protein helps cancer cells avoid programmed death that happens in normal cells and therefore helps cancer cells to stay alive. Blocking BCL2 could help kill MCL cells and make MCL shrink.300 participants will be randomised (having an equal chance like flipping a coin) to receive either sonrotoclax in combination with zanubrutinib (Arm A) or sonrotoclax-matched placebo in combination with zanubrutinib (Arm B). This is a double-blind study which means that neither the participant nor the study doctors will know which treatment Arm a participant has been assigned to.Starting Cycle 1 Day 1, all participants will start zanubrutinib (taken orally) at a dose of 320 mg once daily or 160 mg twice daily until progressive disease, unacceptable side-effects or they are told to stop. On Cycle 2 Day 1, sonrotoclax (Arm A participants) / sonrotoclax-matched placebo (Arm B participants) will start (taken orally) once daily using the twice-a-week ramp-up schedule (where the dose is increased) until the target dose of 320 mg is reached until Cycle 25 Day 28. A cycle is 28 days. Participation in the study is likely to last about 60 months and involve 32-38 visits.
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