Phase 1/2 golcadomide (CELMoD cereblon E3 ligase modulator) + rituximab (CD20 mAb) in R/R MCL

This Phase 1/2 City of Hope trial evaluates golcadomide plus rituximab for relapsed/refractory mantle cell lymphoma in patients resistant or intolerant to covalent BTK inhibitors. Golcadomide (CC-99282; a Bristol Myers Squibb/Celgene CELMoD) binds cereblon (CRBN) within the CRL4 E3 ubiquitin ligase complex and acts as a “molecular glue” to drive degradation of IKZF1/IKZF3 (Ikaros/Aiolos), aiming to boost tumor cell killing and immune activity; rituximab targets CD20 on malignant B cells to promote immune-mediated clearance. Phase 1 gives golcadomide alone (oral daily, days 1–14 of 28-day cycles) to establish safety and dose; Phase 2 adds IV rituximab (weekly in cycle 1, then day 1 of even cycles) to test preliminary efficacy. The scientific angle is whether a next-generation cereblon modulator can “re-sensitize” post-cBTKi MCL to antibody-based therapy with an all-chemotherapy-free backbone. Today’s care after covalent BTK inhibitor failure often shifts to CAR T-cell therapy (when eligible), non-covalent BTK inhibitors, bispecific antibodies in some settings, or combination chemoimmunotherapy, with outcomes still variable—this trial explores a targeted, outpatient oral + antibody regimen.