Sonrotoclax — Drug Monograph

Brand names: Beqalzi

Drug class: BCL-2 Inhibitor

Mechanism of Action

Oral next-generation, highly selective BCL-2 inhibitor (BH3-mimetic). Sonrotoclax binds the anti-apoptotic protein BCL-2 with greater affinity and selectivity over BCL-XL and BCL-W than venetoclax, displacing pro-apoptotic effectors (BIM, BAX/BAK) to restore intrinsic apoptosis in BCL-2-dependent malignancies. Its enhanced selectivity may reduce BCL-XL-mediated thrombocytopenia and retain activity against BCL-2 binding-domain mutations (e.g., G101V) that confer venetoclax resistance.

FDA Indications

• Relapsed or refractory mantle cell lymphoma (MCL) in adults after at least two lines of systemic therapy, including a BTK inhibitor (accelerated approval May 13, 2026; BGB-11417-201 Phase 1/2: ORR 52%, CR 16%, median DOR 15.8 months)

Common Side Effects

• Pneumonia
• Fatigue
• Neutropenia
• Lymphopenia
• Diarrhea
• Anemia
• Thrombocytopenia

Clinical Pearl

Sonrotoclax is the first-and-only BCL-2 inhibitor approved for relapsed/refractory mantle cell lymphoma, filling the post-BTK-inhibitor gap. Like venetoclax, it requires a TLS-mitigating dose ramp-up - but its greater BCL-2 selectivity may cause less thrombocytopenia and may overcome venetoclax-resistant BCL-2 mutations. It is dosed as a once-daily single agent in MCL (distinct from the venetoclax combinations used in CLL).

Related Therapies & Mechanisms

• Venetoclax (Venclexta) — BCL-2 Inhibitor · Lymphoma
• Acalabrutinib (Calquence) — Lymphoma
• Alemtuzumab (Campath) — Lymphoma
• Axicabtagene ciloleucel (Yescarta) — Lymphoma