mezigdomide (CC-92480) / BMS - LARVOL DELTA

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting. (PubMed, Biomark Res) - "Key updates include: Cevostamab (FcRH5×CD3) demonstrated a 30.2% overall response rate in patients who underwent BCMA-targeted treatment and 60.6% in BCMA-targeted naïve patients;the triple-step dosing strategy reduced cytokine release syndrome. Lisaftoclax (APG-2575, BCL-2 inhibitor) displayed overall response rates ranging from 61.3 to 100% and ≥ VGPR rates of 32.3-100%, supporting enhanced response depth with favorable safety in combination regimens. Inobrodib (CCS1477, p300/CBP inhibitor) plus lenalidomide achieved a 71% overall response rate in pomalidomide-refractory patients, marking the first oral epigenetic modulator to reverse immunomodulatory drug resistance. Elranatamab (ELRA, BCMA×CD3) combined with carfilzomib and dexamethasone yielded an 83.3% overall response rate with a median duration of response not reached. Mezigdomide (MEZI, CELMoD) showed an 85.7% overall response rate and 17.5-month progression-free survival in..."

Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

MAGENTA: Mezigdomide and Talquetamab in Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

MEZIGDOMIDE (MEZI) IN NOVEL COMBINATIONS FOR RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED RESULTS FROM THE CA057-003 TRIAL (EHA 2025) - P1/2 | "The CA057-003 phase 1/2 trial (NCT05372354) is evaluating all-oral, novel targeted triplet combination regimens using a MEZI + dexamethasone (DEX) (MEZId) backbone in RRMM, plus EZH2 inhibitor tazemetostat (TAZ), BET inhibitor BMS-986158, or MEK inhibitor trametinib (TRAM). MEZId combined with the novel therapeutic agents TAZ, BMS-986158, or TRAM showed promising efficacy and safety in RRMM. These results provide a rationale for further exploration of these novel all-oral combinations"

Multiple Myeloma • Neutropenia • Plasmacytoma • IKZF1

MEZIGDOMIDE (MEZI) IN NOVEL COMBINATIONS EFFECTIVELY REACTIVATES IMMUNE SYSTEM IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) INCLUDING THOSE AFTER T-CELL-REDIRECTING THERAPIES (EHA 2025) - P1/2 | "MEZI + dexamethasone (MEZId) in combination with novel agents, such as tazemetostat (TAZ), the bromodomain inhibitor (BETi) BMS-986158, and trametinib (TRAM) showed promising efficacy and safety in the phase 1/2 CA057-003 trial (NCT05372354) in pts with RRMM, including those post-TCRT...Last regimen included TCRT for 28 pts (BCMA CAR-T, n=8; GPRC5D CAR-T, n=6; BCMA TCE, n=3; GPRC5D TCE, n=8, BCMA TCE+GPRC5D TCE, n=2; trispecific T-cell-activating constructs, n=1), or various non-TCRT regimens for the other 28 pts... MEZId-based novel combinations lead to activation of adaptive and innate immune populations in pts with RRMM irrespective of prior TCRT exposure. Dynamics of immune changes upon tx with MEZId-based novel combinations is concordant with findings reported for the MEZId backbone. These results suggest previous exposure to TCRT and the addition of novel agents do not affect the ability of MEZI to increase activation and proliferation of NK and T cells,..."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • B3GAT1 • CCR7 • CD8 • HAVCR2 • IKZF1 • IL2RA • IL7R

TRIAL IN PROGRESS: PHASE I/II STUDY OF MEZIGDOMIDE AND ELRANATAMAB FOR RELAPSED/ REFRACTORY MULTIPLE MYELOMA PATIENTS (MELT-MM) (EHA 2025) - P1/2 | "Participants will receive mezigdomide at RP2D -1 dose until confirmed PD by investigator, unacceptable toxicity as assessed by the investigator and/or withdrawal of consent (Figure A).Key inclusion criteria include age ≥ 19 years with ECOG performance status ≤ 2, and measurable disease, 2 prior lines of antimyeloma therapy including lenalidomide and at least 1 proteasome inhibitor. As of January 19, 2025, 3 patients have been enrolled to Part 1 Cohort 1. This trial is registered at ClinicalTrials.gov (NCT06645678)."

Clinical • IO biomarker • P1/2 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • IKZF1

HP-001, AN ORAL IKZF 1/3 MOLECULAR GLUE, DEMONSTRATED SUPERIOR DEGRADATION POTENCY AND SPECIFITY IN THE PRE-CLINICAL MODEL (EHA 2025) - "Background: Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide, which hijack the CRBN E3 ligase to degrade IKZF1/3, remain central to hematologic malignancy treatment...Pre-clinical studies demonstrate HP-001's superior degradation potency and selectivity compared to approved IMiDs and next-generation candidates (e.g., mezigdomide, iberdomide, golcadomide, et al), overcoming resistance mechanisms while minimizing off-target effects... HP-001 is a highly potent and specific degrader of IKZF1/3, with marked antitumor activity as a single agent and in combination with dexamethasone. HP-001 is currently in phase 1 clinical trial for a variety of hematologic malignancies. CDE registration number: CTR20242943."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • CRBN • IKZF1

MEZIGDOMIDE (MEZI) PLUS DEXAMETHASONE (DEX) AND BORTEZOMIB (BORT) OR CARFILZOMIB (CFZ) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED RESULTS FROM THE CC-92480-MM-002 TRIAL (EHA 2025) - P1/2 | "Eligible patients (pts) had RRMM, 2-4 (Cohorts A and C) or 1-3 (Cohort D) prior regimens including lenalidomide, progressive disease (PD) during/after last therapy, and provided informed consent. With longer follow-up, MeziVd and MeziKd confirmed promising efficacy with sustained PFS and a manageable safety profile in RRMM. These results informed ongoing and planned phase 3 trials."

Clinical • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia

MAGNETISMM-30: A PHASE 1B, OPEN-LABEL STUDY OF ELRANATAMAB IN COMBINATION WITH IBERDOMIDE IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) (EHA 2025) - P1 | "Key exclusion criteria are patients with stem cell transplant ≤12 weeks prior to enrollment; active, uncontrolled infection; prior treatment with BCMA-directed or CD3 redirecting therapy or prior CELMoD agents (i.e., IBER or mezigdomide). Clinical trial information: NCT06215118. Study funding: Pfizer."

Clinical • Combination therapy • P1 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Based on the results of early studies, mezigdomide is being evaluated in multiple phase 3 studies (Businesswire) - "SUCCESSOR-1: mezigdomide, bortezomib, and dexamethasone vs. pomalidomide, bortezomib, and dexamethasone in patients with RRMM (projected data in 2026); SUCCESSOR-2: mezigdomide, carfilzomib, and dexamethasone vs. carfilzomib and dexamethasone in patients with RRMM (projected data in 2026)"

P3 data • Multiple Myeloma

Abstract #4160130: Updated results were presented from the dose-escalation phase of the MM-002 study for the combinations of mezigdomide, dexamethasone, and bortezomib (Cohort A MeziVd; n=28), and mezigdomide, dexamethasone, and carfilzomib (Cohort C MeziKd; n=27) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2–4 prior therapies (Businesswire) - P1/2 | N=424 | NCT03989414 | Sponsor: Celgene | "Overall response rate (ORR) was 75.0% for Cohort A and 85.2% for Cohort C, respectively. Median (95% CI) duration of response (DOR) for Cohort A and Cohort C was 10.9 (8.8–18.7) and 11.9 (6.4–35.9) months, respectively. Median (95% CI) progression-free survival (PFS) for Cohort A and Cohort C was 12.3 and 13.5 months, respectively. Results from the dose-expansion cohort (Cohort D) of the study were also presented for the MeziVd combination (n=49) in patients with RRMM who had received 1–3 prior therapies: ORR was 85.7%; Median (95% CI) DOR was 19.4 months (9.7-NA); Median PFS (95% CI) was 17.5 months"

P1/2 data • Multiple Myeloma

Abstract #4160802: New data was presented evaluating mezigdomide in all-oral triplet combinations with other oral novel agents in RRMM (Businesswire) - P1b/2a | N=160 | NCT05372354 | Sponsor: Bristol-Myers Squibb | "Results showed that the ORR was: 50% for mezigdomide plus EZH2 inhibitor tazemetostat and dexamethasone (n=16) 35% for mezigdomide plus BET inhibitor BMS-986158 and dexamethasone (n=20) 80% for mezigdomide plus MEK inhibitor trametinib and dexamethasone (n=20) The most frequent grade 3/4 TEAE was neutropenia, and grade 3/4 nonhematologic TEAEs were low...A separate analysis (Abstract #4160749) showed that these combinations lead to the activation and proliferation of NK and T cells, including in patients previously treated with T cell-redirecting therapies."

P1/2 data • Multiple Myeloma

ASCOmind: Is instant ASCO abstract analysis possible with AI agents? (ASCO 2025) - "ASCOmind generated a treatment distribution table for RRMM and NDMM (Table 1), with one misclassification corrected by humans-Mezigdomide reclassified from ADC to the correct category... Our preliminary analysis of ASCOmind demonstrated high accuracy and efficiency in automating abstract analysis, enabling rapid analysis of trends and outcomes. This feasibility study highlights the scalability of AI systems across all cancer types, supporting decision-making. Treatment distribution in RRMM and NDMM studies."

Hematological Malignancies • Multiple Myeloma • Oncology

MagnetisMM-30: A phase 1b, open-label study of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma (RRMM). (ASCO 2025) - P1 | "Key exclusion criteria are pts with stem cell transplant ≤12 weeks prior to enrollment; active, uncontrolled infection; prior treatment with BCMA-directed or CD3 redirecting therapy or prior CELMoD agents (ie, IBER or mezigdomide)...Secondary endpoints include AEs and lab abnormalities (Part 1 only), ORR, CRR, time-to-event outcomes, pharmacokinetics, minimal residual disease negativity rate, and immunogenicity. This study is ongoing; Part 1 and Part 2 will enroll up to approximately 36 and 60 pts, respectively."

Clinical • Combination therapy • P1 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

A Study to Evaluate the Drug Levels of Mezigdomide in Adult Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Celgene | Recruiting ➔ Completed | Trial completion date: Mar 2025 ➔ Nov 2024 | Trial primary completion date: Mar 2025 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease

Expanded Access for Mezigdomide (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Bristol-Myers Squibb

New trial

A Study to Determine the Recommended Dose and Schedule, and Evaluate the Safety and Preliminary Efficacy of Mezigdomide in Combination With Elranatamab in Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=62 | Not yet recruiting | Sponsor: Celgene

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Mezigdomide, Carfilzomib, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma in Patients With Extramedullary Disease (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Roswell Park Cancer Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

HP-001: A highly potent IKZF1/3 degrader that demonstrates superior safety profile (AACR 2025) - "IMiDs (e.g. pomalidomide, CC-220, CC-92480. HP-001 is a highly potent, catalytic degrader of IKZF1/3, with marked antitumor activity as a single agent and in combination with dexamethasone. HP-001 is currently in phase 1 clinical trial (CDE registration number: CTR20242943), a first-in-human, open-label, multicenter study to evaluate it as monotherapy in patients with r/r MM or NHL."

Clinical • Late-breaking abstract • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN • GSPT1 • IKZF1 • SALL4

A Study to Evaluate Alnuctamab in Combination With Mezigdomide in Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=156 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Aug 2025 ➔ May 2025

Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Can we develop effective direct or indirect inhibitors of transcription factors? On the clinical evolution of protein degraders for multiple myeloma therapy. (PubMed, Expert Opin Ther Targets) - "Preclinical data on PROTACs are promising. Nevertheless, a deeper understanding of TF biology as well as further advancements in screening methodologies and chemoproteomics are crucial to further spur the transformative potential of targeted TF degradation in MM."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • CRBN • IKZF1 • IKZF3

Elotuzumab, CC-92480, and Dexamethasone for the Treatment of Relapsed or Refractory Myeloma After CD38- and BCMA-Targeted Therapies (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Abdullah Khan | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Mezigdomide, Carfilzomib, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma in Patients With Extramedullary Disease (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Nov 2029 ➔ Apr 2030 | Trial primary completion date: Nov 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Mezigdomide: Data readout from P3 SUCCESSOR-1 trial (NCT05519085) for 2L multiple myeloma in 2026 (Bristol-Myers Squibb) - Q4 2024 Results: Data from P3 SUCCESSOR-2 trial (NCT05552976) for 2L multiple myeloma in 2026

P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Preliminary Efficacy, Safety Data Drive Further Exploration of Mezigdomide-Based Combinations in R/R Myeloma (OncLive) - P1b/2a | N=220 | NCT05372354 | Sponsor: Bristol-Myers Squibb | "In a presentation at the 2024 ASH Annual Meeting & Exposition, results from CA057-003 showed that mezigdomide in combination with either the EZH2 inhibitor tazemetostat (n = 16), the BET inhibitor BMS-986158 (n = 20), or the MEK inhibitor trametinib (Mekinist; n = 20) elicited overall response rates of 50%, 35% or 75%, respectively. Notably, trends towards deeper responses, evidenced by the rates of very good partial response or better, were observed with the 1.0 mg dose of mezigdomide in the tazemetostat and BMS-986158 cohorts. In the trametinib cohort, deeper responses were reported at mezigdomide doses of 0.6 mg or higher; 11 patients at the 1.0 mg dose level (n = 13) continued treatment. No new safety signals were identified across all cohorts."

P1/2 data • Multiple Myeloma