Phase 2 BOSon tests zanubrutinib + obinutuzumab + sonrotoclax in frontline MCL

Memorial Sloan Kettering Cancer Center is running this Phase 2 study of a chemotherapy-free, MRD-guided frontline regimen for transplant-ineligible patients with stage II–IV mantle cell lymphoma. Treatment combines zanubrutinib, a Bruton tyrosine kinase (BTK) inhibitor, with obinutuzumab, an anti-CD20 monoclonal antibody, and sonrotoclax (Beqalzi/BGB-11417), a BCL-2 inhibitor, with sonrotoclax introduced using a dose ramp-up beginning in cycle 2 to reduce tumor lysis risk. Minimal residual disease (MRD) testing helps guide treatment duration, with the goal of achieving deep remissions while avoiding indefinite therapy. Sonrotoclax received FDA accelerated approval in May 2026 for relapsed/refractory MCL after at least two prior systemic therapies including a BTK inhibitor, making this an early effort to move the drug from later-line disease into a chemotherapy-free frontline combination. For transplant-ineligible patients, current frontline options include bendamustine/rituximab-based therapy, including FDA-approved acalabrutinib + bendamustine/rituximab; BOSon asks whether combining BTK, BCL-2, and CD20 targeting can deliver deep, MRD-negative responses without conventional chemotherapy.