The Babak Lab shared on LinkedIn:
“Clinical Mondays: Is targeted protein degradation ready to compete with established cancer therapies?
The latest Phase 3 data suggest the answer may be yes.
Results from the SUCCESSOR-2 trial have put mezigdomide in the spotlight. Unlike many oncology drugs that find new indications over time, mezigdomide is an entirely new CELMoD (cereblon E3 ligase modulator) designed to harness the cell’s own protein degradation machinery.
By promoting the degradation of the transcription factors Ikaros and Aiolos, it targets proteins that multiple myeloma cells depend on for survival.
The Phase 3 trial evaluated MeziKd versus standard Kd in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide and an anti-CD38 antibody.
Key Insights (479 patients):
- mPFS doubled: 18.0 vs 8.3 months (HR 0.48).
- ORR: 80.2% vs 53.4%.
- ≥CR: 26.7% vs 8.9%.
- The benefit was maintained across high-risk subgroups.
- Grade 3–4 neutropenia (61%) and infections (34%) were more frequent but manageable.
Conclusion:
For clinicians, MeziKd represents a strong new option for patients at first relapse after lenalidomide and anti-CD38 therapy, although careful management of hematologic toxicity will remain important.
More broadly, these Phase 3 results show that targeted protein degradation can deliver meaningful clinical benefit in a large randomized trial and is no longer just an intriguing laboratory concept. Mezigdomide is now a serious contender to watch in the multiple myeloma treatment landscape.”
Title: Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): Results from the phase 3 SUCCESSOR-2 trial
Authors: Paul G. Richardson, Fredrik Schjesvold, Chengcheng Fu, Monique A. Hartley-Brown, Cesar Gomez, Donna Ellen Reece, Gabor Mikala, Omar Alkharabsheh, Christopher Parrish, Darrell White, Hang Quach, Claudio Cerchione, Vania Hungria, Amitabha Mazumder, Marc S. Raab, Albert Oriol Rocafiguera, Zehua Zhou, Alberto Rocci, Brian Yu, and Meletios A. Dimopoulos.
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