iberdomide (CC-220) / 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

EXCALIBER: Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=864 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

CC-220-DLBCL-001: Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma (clinicaltrials.gov) - P1 | N=174 | Recruiting | Sponsor: Celgene | Trial completion date: Jun 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

GOLSEEK-1: A PHASE 3, DOUBLE-BLIND, RANDOMIZED STUDY OF GOLCADOMIDE + R-CHOP VERSUS PLACEBO + R-CHOP IN PATIENTS WITH PREVIOUSLY UNTREATED, HIGH-RISK, LARGE B-CELL LYMPHOMA (ICML 2025) - P3 | "Introduction: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard treatment (Tx) for diffuse large B-cell lymphoma (DLBCL) and is curative in ≈60–70% of patients (pts)...In the phase 1b study CC-220-DLBCL-001, GOLCA + R-CHOP was well tolerated, with promising activity and combinability and high rates of durable responses irrespective of COO in pts with previously untreated aggressive BCL, including HR pts...Key secondary endpoints include PFS in non–high-grade BCL, event-free survival, independently assessed complete metabolic response, undetectable minimal residual disease by PhasED-Seq, and overall survival. This study is recruiting globally at 309 sites in 36 countries."

Clinical • P3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • CRBN • IKZF1

Testing the Combination of Two Approved Drugs and One Experimental Drug in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=88 | Suspended | Sponsor: Alliance for Clinical Trials in Oncology | Not yet recruiting ➔ Suspended

Trial suspension • Hematological Malignancies • Multiple Myeloma • Oncology

MINIMAL RESIDUAL DISEASE-DRIVEN STRATEGY FOLLOWING ISATUXIMAB-CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE INDUCTION IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PRIMARY ENDPOINTS OF THE PHASE 3 MIDAS TRIAL (EHA 2025) - P3 | "MRD- positive patients after induction (MRD ≥10−5) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance. After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10−5, MRD negativity rates at 10−6 before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10-5, tandem ASCT did not significantly improve MRD negativity rates at 10−6 before maintenance. Further follow-up, including sustained MRD negativity and PFS data, is needed to evaluate the long-term outcomes of this MRD-adapted strategy."

Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

IBERDOMIDE AND DEXAMETHASONE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (EHA 2025) - "Background: Iberdomide (Iber) is a cereblon E3 ligase modulator (CELMoD) with more potent tumoricidal and immune-stimulatory effects compared to lenalidomide and pomalidomide...After LenDex plus daratumumab became a standard of care, the IberDex arm was closed, having enrolled 18 pts... In this frail, elderly MM cohort, IberDex showed notable and sustained efficacy, with only two progressions after nearly two years of follow-up. Toxicity was manageable, with low rates of non-hematologic AEs, and severe infections mainly occurring in older, frail patients receiving 1.6 mg."

Clinical • Anemia • Febrile Neutropenia • Geriatric Disorders • Infectious Disease • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN

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

IBERDOMIDE, BORTEZOMIB, AND DEXAMETHASONE (IBERVD) IN TRANSPLANT-INELIGIBLE (TNE) NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): UPDATED RESULTS FROM THE CC-220-MM-001 TRIAL (EHA 2025) - P1/2 | "Background: Lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX) are recommended for NDMM. With longer follow-up (13–25 months), IberVd confirmed durable deep responses, with ≥ CR % rising from 56.3% to 75.0%, and an encouraging safety profile with no new signals in pts with TNE NDMM. These data support IberVd evaluation in the frontline setting"

Fatigue • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation

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

IBERDOMIDE (IBER) TREATMENT ENHANCES MANUFACTURED CAR T CELL EXPANSION AND FUNCTIONALITY AND IS IMMUNOSTIMULATORY IN PATIENTS POST-CAR T CELL THERAPY (EHA 2025) - P1/2 | "Peripheral blood samples were collected from pts receiving IBER (1.6 mg) and dexamethasone (DEX) in the CC-220-MM-001 (NCT02773030) study prior to Tx initiation and after 1 cycle. Our results provide rationale for IBER as an adjunctive therapy to CAR T cell therapy to improve responses in RRMM. IBER+DEX Tx of pts enhanced the proliferation, expansion, and functionality of manufactured CAR T cells. Our findings suggest that Tx of pts with IBER prior to apheresis may improve T cell expansion, manufacturing success, and potency of infused CAR T cells."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CD28 • CD38 • CD4 • GZMB • HAVCR2 • IKZF1 • PD-1 • TIGIT • TNFA

Based on the results of early studies…iberdomide is being evaluated in multiple phase 3 studies (Businesswire) - "EXCALIBER RRMM: iberdomide, daratumumab, and dexamethasone vs. daratumumab, bortezomib, and dexamethasone in patients with RRMM (projected MRD data in 2025); EXCALIBER Maintenance: iberdomide maintenance vs. lenalidomide maintenance following autologous stem cell transplant in patients with NDMM (projected data in 2029)"

P3 data • Multiple Myeloma

Abstract #4160144: Updated results were presented from MM-001, evaluating the combination of iberdomide, bortezomib, and dexamethasone (IberVd) in patients with transplant-ineligible, newly diagnosed multiple myeloma (NDMM), confirming durable, deep responses in the study (Businesswire) - P1b/2a | N=466 | NCT02773030 | Sponsor: Celgene | "At a median follow-up of 25 months, the ORR in the intent-to-treat (ITT) population (n=18) was 88.9%, with 66.6% having a complete response or better. 44% of patients in CR achieved minimal residual disease (MRD) negativity at a sensitivity of 10-5. The most common hematologic grade 3/4 TEAE was neutropenia (29.4%); 2 (11.8%) patients had grade 3/4 peripheral neuropathy. Overall, the most common grade 3/4 TEAEs were infections (47.1%)."

P1/2 data • Multiple Myeloma

MRD-driven strategy following IsaKRD induction in transplant-eligible NDMM: Primary endpoints of the phase 3 MIDAS trial. (ASCO 2025) - P3 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT04934475 Background: The phase III IFM2020-02-MIDAS study (NCT04934475) evaluated a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM)...MRD-positive patients after induction (MRD ≥10⁻⁵) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance... After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10⁻⁵, MRD negativity rates at 10⁻⁶ before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10-5, tandem ASCT did not significantly improve MRD negativity rates at 10⁻⁶..."

P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Iberdomide, bortezomib, and dexamethasone (IberVd) in transplant-ineligible (TNE) newly diagnosed multiple myeloma (NDMM): Updated results from the CC-220-MM-001 trial. (ASCO 2025) - P1/2 | "Funded by Bristol Myers Squibb Clinical Trial Registration Number: NCT02773030 Background: Lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX) are recommended for NDMM. With longer follow-up (13–25 mo), IberVd confirmed durable deep responses, with ≥ CR % rising from 56.3% to 75.0%, and an encouraging safety profile with no new signals in pts with TNE NDMM. These data support IberVd evaluation in the frontline setting."

Fatigue • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation

Carfilzomib, iberdomide, and dexamethasone (KID) in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): Updated results from phase 1/2 study. (ASCO 2025) - P1/2 | "Iberdomide, a cereblon modulator, enhances immune stimulatory activity in vitro compared to thalidomide analogs... Induction therapy with KID appears safe and effective leading to deep responses and adequate stem cell collection despite short tx duration and 42% harboring high-risk cytogenetics. Long-term follow-up is needed to determine durability of response. Correlative studies are underway to evaluate immune phenotype and microbiome changes pre/post-tx."

Clinical • P1/2 data • Anemia • Dermatology • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Pruritus • Thrombocytopenia • Transplantation • CRBN • TP53

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

Targeted Degradation of Mutant p53 Reverses the Pro-oncogenic Dominant-Negative Effect. (PubMed, Cancer Res) - "In experiments whereby mutant p53 was degraded using a degron-tagged construct combined with iberdomide as a molecular glue, remarkable therapeutic efficacy was observed when this approach was used in combination with an MDM2 inhibitor. This work paves the way for therapeutic strategies that aim to degrade mutant p53 proteins in cases in which a WT TP53 allele is retained. See related article by Klemm et al., p. 1978."

Journal • Oncology • Targeted Protein Degradation • TP53

Study of Iberdomide in People With Multiple Myeloma Who Have Had an Autologous Hematopoietic Stem Cell Transplant (AHCT) (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | N=86 ➔ 16 | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

KarMMa-7: Safety and Efficacy of bb2121 (Ide-cel) Combinations in Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=21 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed | N=312 ➔ 21

Enrollment change • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Iberdomide Maintenance Therapy in Patients With Multiple Myeloma (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: University of Nebraska | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2025 ➔ Jan 2026

Enrollment closed • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma. (PubMed, Future Oncol) - P3 | "Multiple myeloma (MM) is a plasma cell neoplasm that stems from the malignant transformation of clonal plasma cells. In a phase I/II trial, IBER in combination with DARA and DEX (IberDd) was well tolerated and demonstrated promising preliminary efficacy in patients with heavily pretreated RRMM, including patients refractory to IMiD agents, DARA, and proteasome inhibitors. EXCALIBER-RRMM is a unique confirmatory phase III trial that incorporates a 2-stage seamless design to firstly address dose optimization of IberDd, and secondly, to compare the efficacy and safety of the selected IberDd dose with DARA, bortezomib, and DEX in patients with early-line (1 or 2 prior lines of therapy) RRMM.Clinical trial registration: www.clinicaltrials.gov identifier is NCT04975997."

Journal • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Thomas Martin, MD | Trial completion date: Jun 2028 ➔ Jun 2029 | Trial primary completion date: Jun 2026 ➔ Jun 2027

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

A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas (clinicaltrials.gov) - P1 | N=62 | Terminated | Sponsor: Celgene | Completed ➔ Terminated; Business objectives have changed.

Trial termination • B Cell Lymphoma • Classical Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • BCL2 • BCL6

Model-informed Drug Development (MIDD) Approach to Support Biopharmaceutical Development of Iberdomide. (PubMed, AAPS J) - "Sensitivity analysis using the PBPK model demonstrated that iberdomide permeability and total amount of drug released from formulation are the most sensitive parameters in defining the systemic exposure of iberdomide, in agreement with iberdomide's BCS III classification where drug release from drug product, and not solubility, is the rate-limiting step of dissolution. Based on the totality of evidence, which included clinical and in vitro data supplemented by modeling and simulation, no food effect is expected with the ICF."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology