Targeted Protein Degradation: Clinical Advancements in Multiple Myeloma
The treatment landscape for relapsed or refractory multiple myeloma (RRMM) continues to evolve with the development of targeted protein degradation (TPD) therapies. As evidenced by the layout discrepancies and raw code blocks shown in the previous framework ({FBB09FAD-6A4F-47B9-ADAF-21FAE52D0054}.png), presenting this clinical data requires a streamlined, objective structure. This analysis outlines the documented clinical parameters for two prominent assets in this space: Bristol Myers Squibb’s mezigdomide and C4 Therapeutics’ cemsidomide.
1. Bristol Myers Squibb: Mezigdomide (CC-92480)
Mezigdomide is an oral cereblon E3 ligase modulation (CELMoD) agent designed to promote targeted protein degradation. It is currently being evaluated in late-stage clinical settings against standard-of-care regimens.
Efficacy Data (SUCCESSOR-2 Trial)
Bristol Myers Squibb recently announced findings from the Phase 3 SUCCESSOR-2 trial (NCT05552976), which evaluated mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) against a control arm of carfilzomib and dexamethasone (Kd) alone.
- Progression-Free Survival (PFS): The MeziKd combination demonstrated a median PFS of 18 months, compared to 8.3 months for the Kd arm.
- Risk Reduction: This result represented a 52% reduction in the risk of disease progression or death compared to the control regimen.
- Response Metrics: The overall response rate (ORR) for MeziKd was 80.2%, versus 53.4% for Kd.
- Complete Response: A complete response or better was achieved by 26.7% of patients receiving MeziKd, compared to 8.9% of patients in the Kd arm.
2. C4 Therapeutics: Cemsidomide (CFT7455)
Cemsidomide is an orally bioavailable small molecule degrader targeting the IKZF1/3 transcription factors, which are known drivers of multiple myeloma.
Efficacy Data (CFT7455-1101 Trial)
Cemsidomide is being investigated in the ongoing open-label Phase 1/2 CFT7455-1101 study (NCT04756726) in combination with dexamethasone.
- Recent Dose Evaluations: Based on an April 30, 2025 data cutoff, a 100 µg once-daily dose resulted in an ORR of 50% among 10 evaluable patients.
- Alternative Dosing: A 75 µg once-daily dose yielded an ORR of 40% across a cohort of 20 evaluable patients.
- Prior Cutoff Baselines: An earlier data analysis from October 11, 2024, indicated a 26% ORR and a 40% clinical benefit rate among 42 patients analyzed across all evaluated dose levels.
TOTAL EXTRACTED3
RECRUITING STATUS2
COMPLETED RUNS0
➔
Multiple MyelomaRelapsed/Refractory Multiple Myeloma
N=100Est. Finish: 2030-03
A Study to Evaluate the Efficacy of Cemsidomide + Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma
recruiting
ENROLLMENT PATIENT CAPACITY100 Patients(estimated)
ESTIMATED RUN COMPLETION MILESTONESStart Date:2026-02-18(actual)
Primary End:2030-03(estimated)
Study Finish:2030-03(estimated)
OFFICIAL PROTOCOL TITLEA Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy of Cemsidomide + Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma
Binod Dhakal, M.D.PRINCIPAL INVESTIGATOR — Medical College of Wisconsin
Martin Kaiser, M.D.PRINCIPAL INVESTIGATOR — The Royal Marsden
Aurore Perrot, M.D.PRINCIPAL INVESTIGATOR — Universite de Toulouse
James Berenson, MDCONTACT — Berenson Cancer Center
Andrew Sochacki, MDCONTACT — START Midwest
Kyriakos Papadopoulos, MDCONTACT — START San Antonio
Overall response rate (ORR) per International Myeloma Working Group (IMWG) Response Criteria by an Independent Review Committee (IRC)Analysis Window: up to approximately 43 months
Duration of response (DoR; IRC assessed)Analysis Window: up to approximately 43 months
Complete response (CR) rate (IRC assessed)Analysis Window: up to approximately 43 months
Time to response (IRC assessed)Analysis Window: up to approximately 43 months
Progression free survival (PFS; IRC assessed)Analysis Window: up to approximately 43 months
Overall survival (OS)Analysis Window: up to approximately 43 months
Adverse events (AEs); serious AEs (SAEs); AEs leading to treatment interruption, reduction, or discontinuation; and deathsAnalysis Window: within 30 to 35 days of the last dose of study treatment
Plasma concentrations of cemsidomideAnalysis Window: up to approximately 4 months
Cemsidomide + Dexamethasone:EXPERIMENTAL
Participants receive cemsidomide plus dexamethasone during a 28-day treatment cycle, and will continue to receive treatment until the participant meets one of the discontinuation criteria.
CemsidomideDRUG
dosed orally (PO) once a day (QD) 14 days on/14 days off for each 28-day cycle
DexamethasoneDRUG
dosed PO once a week (QW) on Days 1, 8, 15, and 22 for each 28-day cycle
➔
N=60Est. Finish: 2029-06
A Study to Learn About the Effects of Cemsidomide in Combination With Elranatamab in Relapsed/Refractory Multiple Myeloma Subjects
recruiting
ENROLLMENT PATIENT CAPACITY60 Patients(estimated)
ESTIMATED RUN COMPLETION MILESTONESStart Date:2026-02-06(actual)
Primary End:2028-12(estimated)
Study Finish:2029-06(estimated)
OFFICIAL PROTOCOL TITLEA Phase 1B, Open-label, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of Cemsidomide in Combination With Elranatamab in Relapsed/Refractory Multiple Myeloma Subjects
Study Medical OfficerCONTACT — C4 Therapeutics, Inc.
Safety and tolerability of cemsidomide in combination with elranatamabAnalysis Window: Cycle 1 approximately 28 days
Safety and tolerability of cemsidomide in combination with elranatamabAnalysis Window: Baseline through 30 days after discontinuation of study treatment
Assess antimyeloma activityAnalysis Window: Approximately 2 years
Evaluate the PK of cemsidomide and elranatamabAnalysis Window: Approximately 4 months
Evaluate the PK of cemsidomide and elranatamabAnalysis Window: Approximately 2 years
Assess the immunogenicity of elranatamabAnalysis Window: Approximately 2 years
Non-randomized cemsidomide (tablet) plus elranatamab (subcutaneous injection)EXPERIMENTAL
No descriptive logs found.
CemsidomideDRUG
IKZF1/3 degrader
ElranatamabBIOLOGICAL
• BCMA-CD3 bispecific antibody
➔
Multiple MyelomaLymphoma, Non-Hodgkin's
N=224Est. Finish: 2026-12-31
Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma
active not recruiting
ENROLLMENT PATIENT CAPACITY224 Patients(estimated)
ESTIMATED RUN COMPLETION MILESTONESStart Date:2021-04-27(actual)
Primary End:2026-09-30(estimated)
Study Finish:2026-12-31(estimated)
OFFICIAL PROTOCOL TITLEA Phase 1/2 Open-Label Multi-Center Study to Characterize the Safety and Tolerability of CFT7455 in Subjects With Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma
// NO_EXPLICIT_INVESTIGATORS_OR_ROSTERS_LOGGED
Phase 1: Safety and tolerability of cemsidomideAnalysis Window: Baseline through 30 days after the last dose of study treatment
Phase 1: Safety and tolerability of cemsidomide in combination with dexamethasoneAnalysis Window: Baseline through 30 days after the last dose of study treatment
Phase 1: Maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for cemsidomideAnalysis Window: Days 1-28
Phase 1: MTD or recommended RP2D for cemsidomide in combination with dexamethasoneAnalysis Window: Days 1-28
// NO_EXPLICIT_SECONDARY_OUTCOMES_DUMPED
Phase 1: Arm A - cemsidomideEXPERIMENTAL
Participants with r/r NHL or r/r MM will be treated with oral cemsidomide as a single agent administered at different dosages and dosing schedules.
Phase 1: Arm B1 - cemsidomideEXPERIMENTAL
Participants with r/r MM will be treated with escalating doses of oral cemsidomide as a single agent administered at different dosages and dosing schedules in each cohort, until the determination of maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) or Sponsor discretion.
Phase 1: Arm B2 - cemsidomide in combination with dexamethasoneEXPERIMENTAL
Participants with r/r MM will be treated with escalating doses of oral cemsidomide in combination with a fixed dose of oral dexamethasone in each cohort
Phase 1: Arm C - cemsidomideEXPERIMENTAL
Participants with r/r NHL will be treated with escalating doses of oral cemsidomide single agent administered according to different dosing schedules in each cohort
Phase 2: Arm 1 - cemsidomideEXPERIMENTAL
Participants with r/r MM will be treated with oral cemsidomide single agent
Phase 2: Arm 2 - cemsidomide in combination with dexamethasoneEXPERIMENTAL
Participants with r/r MM treated with oral cemsidomide in combination with oral dexamethasone
Phase 2: Arm 3 - CFT7455EXPERIMENTAL
Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral cemsidomide single agent
cemsidomideDRUG
oral cemsidomide
Dexamethasone OralDRUG
oral dexamethasone \[ ≤75 years old: 40 mg once per week (QW) on days 1, 8, 15, and 22; \>75 Years old: 20 mg QW on days 1, 8, 15, and 22\]
3. Safety and Tolerability Profiles
Both clinical programs closely monitor adverse events (AEs), particularly hematological toxicities, which are common within this drug class.
Mezigdomide Safety Observations
- Grade 3-4 Events: In the SUCCESSOR-2 trial, Grade 3-4 treatment-emergent adverse events were reported in 83.7% of the MeziKd cohort, compared to 56.5% in the Kd cohort.
- Neutropenia: Grade 3-4 neutropenia was observed in 61.1% of patients treated with MeziKd, versus 9.1% for the Kd arm.
- Infections: Infections were noted in 34.0% of the MeziKd group, compared to 15.6% for the Kd group.
Cemsidomide Safety Observations
- Adverse Events: In the Phase 1 trial data from the October 2024 cutoff (among 47 safety-evaluable patients), the most frequently reported Grade 3 or higher adverse effect was neutropenia (n=18).
- Secondary Effects: Additional Grade 3 or higher events included anemia (n=10) and infections (n=8).
- Discontinuations: Investigators reported that no patients discontinued treatment specifically due to neutropenia within this dataset.
4. Summary Matrix of Clinical Programs
The following ledger distills the operational parameters and clinical statuses for both therapeutic assets. Text has been consolidated to preserve UI integrity on digital dashboards.
| Asset | Sponsor | Molecular Target | Clinical Phase | Primary Indication |
|---|
| Mezigdomide (CC-92480) | Bristol Myers Squibb | Cereblon E3 Ligase | Phase 3 | Relapsed/Refractory Multiple Myeloma |
| Cemsidomide (CFT7455) | C4 Therapeutics | IKZF1/3 | Phase 1/2 | Relapsed/Refractory Multiple Myeloma |
Note on Data Interpretation: All clinical response rates, safety metrics, and progression-free survival timelines are drawn directly from published trial cutoffs and corporate disclosures. Cross-trial comparisons should be interpreted with caution due to differences in trial design, patient population, and prior lines of therapy.