iberdomide (CC-220) / BMS - LARVOL DELTA

Lumit-based profiling of degrader dynamics reveals signaling-dependent, cell context-specific sensitivity to degraders (AACR 2026) - "Multiple target-degrader pairs have been validated, including BRD4-ARV-771, IKZF1-Iberdomide, and STAT3-SD-36...While it has been traditionally thought that resistance to TPD therapies can occur due to changes in degrader mechanics or the target protein within the cell, we have demonstrated that intrinsic cellular pathways can impact degrader potency. This discovery may redefine TPD limitations to include signaling-regulated phenotypes."

Oncology • BRD4 • CRBN • IKZF1 • STAT3

Development of a novel Ikaros/Aiolos transcriptional signature and correlation with patient response in multiple myeloma patients treated with CELMoDs (AACR 2026) - "To refine the target list, we investigated transcriptional changes of the Ik targets when exposed to lenalidomide (LEN), pomalidomide (POM), and mezigdomide (MEZI) at 6, 24, and 48-hour timepoints, and iberdomide (IBER) at a 24-hr timepoint. We compiled Ik targets and devised an RNA-seq based Ik activity score that is significantly associated with patient outcome and is comparable with the IHC score."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • CRBN • IKZF1

GMMG-HD9/DSMM XVIII: a randomized phase-III trial assessing iberdomide versus iberdomide plus isatuximab maintenance-therapy post-autologous hematopoietic stem-celltransplantation in patients with newly diagnosed multiple myeloma (OeGHO-AHOP 2026) - "End of study is planned after first HDM/ASCT and includes mandatory response assessment and BMA for all participants. Primary objective: Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates after two years of maintenance therapy."

Clinical • P3 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Transplantation

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=466 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Feb 2028 ➔ Jul 2028

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

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 | Recruiting | Sponsor: Alliance for Clinical Trials in Oncology | Suspended ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

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

A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The rekindle study (ASH 2025) - P2 | "In this context, Iberdomide is a potent cereblon E3 ligase modulator (CELMoD)with demonstrated activity in IMiD-resistant disease (Lonial et al., Lancet Haematology. This quadruplet reinduction strategy adds another treatment alternative in the early relapsesetting (i.e., following lenalidomide resistance; 1-3 prior lines) where parenteral (SC or IV) T-cellredirecting therapies are gaining increased prominence. IberKDd is safe with a manageable toxicityprofile, and it affords the opportunity for de-escalation to oral monotherapy; decreasing the burden ofcontinuous parenteral therapy which is common in this setting of MM."

P2 data • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Myocardial Infarction • Neutropenia • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN

Iberdomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: An update from the phase 2 EMN26 trial (ASH 2025) - P2 | "All pts received a PI/IMiD-containing induction regimen, which also includeddaratumumab in 53% of pts. These data support the investigation of iberdomide versus lenalidomide maintenance inthe ongoing phase 3 registrational EXCALIBER Maintenance trial. The dose of 0.75 mg iberdomide waschosen as the recommended maintenance dose for further evaluation, based on comparable efficacywith superior tolerability, compared to higher doses of iberdomide."

Clinical • P2 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia • Transplantation • Venous Thromboembolism

Interim analysis of efficacy and safety for ALLG MM25 (Viber-M): A phase I b/II study of venetoclax, iberdomide and dexamethasone for patients in first or second relapse of multiple myeloma with t(11; 14) (ASH 2025) - "Given the high attrition rates in patient numbers at each relapse,prioritising effective treatments early in the disease course is vital.In the era of lenalidomide (Len)-based induction and maintenance, there is need for a Len-free regimenat relapse. Iberdomide (Iber) is a potent oral cereblon E3 ligase modulator (CELMoD)...G3/4 TEAEs were reported in 11 patients (55%), with neutropenia being the most common(45%); 12 patients (60%) required filgrastim support...As of data cutoff, 44 of 50 patients have been enrolled. The planned interim analysis was conducted forthe first 20 patients (median age 65 years; range 41-83) following completion of three treatment cycles.Of these, 12 (60%) underwent planned dose escalation over three cycles, and 8 (40%) over two cycles. Themajority (75%) had one prior LOT."

Clinical • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • CRBN

An immune-therapeutic salvage strategy for 'functional' high-risk (FHR) multiple myeloma (MM) incorporating iberdomide, isatuximab, and dexamethasone – the IBIS study amarc 20-01. (ASH 2025) - P2 | "Of 50 pts: 28%, 32%, 16%, 12% with 0, 1, 2 or 3 high-risk chromosomal abnormalitiesrespectively; 34% fulfilling IMS2025 high-risk criteria, 54% standard-risk and 12% in whom diagnosticCG/FISH were omitted, 83% received PI-IMID 1L (76% VRd, 3% VRd+chemotherapy, 7% VRd+Selinexor),10% bortezomib-cyclophosphamide-dexamethasone (VCD), 7% lenalidomide-dexamethasone (Rd), 24%ASCT; 10% 1REF to 1L and 90% relapsed after initial response to 1L, of these 72% had ³PR to 1L. In this second planned interim analysis, IB-IS-DEX was well-tolerated, achieved early diseasecontrol and demonstrated promising efficacy in FHR MM. Preliminary ctDNA genomic analyses highlight asubstantial burden of adverse biology, with frequent del(17p), MYC copy number gains, and high cTFamong pts with PD. Updates on survival will be presented at the conference."

CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Neutropenia • Respiratory Diseases • Septic Shock • Sleep Disorder • Squamous Cell Carcinoma

ICON: Iberdomide Combined With Low-dose Cyclophosphamide and Dexamethasone (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Amsterdam UMC, location VUmc | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial (ASH 2025) - P1, P2 | "The study continuesenrolling and will explore ELRA + IBER in a larger group of pts with RRMM. Results from a longer follow-up will be presented."

Clinical • Combination therapy • P1 data • Anorexia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia

Golcadomide (GOLCA), a potential, first-in-class, oral CELMoD™ agent, plus R-CHOP in patients (Pts) with previously untreated aggressive B-cell lymphoma (a-BCL): 24-month efficacy Results (ASH 2025) - P1, P3 | "GOLCA drivesthe closed, active conformation of cereblon to induce rapid and deep degradation of Ikaros and Aiolos,leading to direct cell killing (agnostic of cell of origin [COO]) and immunomodulatory activity.CC-220-DLBCL-001 (NCT04884035) is an ongoing Phase 1b, open-label, multicenter trial to assess safetyand preliminary efficacy of GOLCA+R-CHOP in previously untreated a-BCL. GOLCA+R-CHOP demonstrated a predictable and manageablesafety profile with low rates of non-hematologic AEs; addition of GOLCA to R-CHOP did not compromiseSOC delivery. These data continue to show that GOLCA 0.4mg, when added to SOC Tx, has a potential tocure more previously untreated pts with HR LBCL and support the ongoing Phase 3 trial, GOLSEEK-1, inthis population (NCT06356129)."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Gastrointestinal Disorder • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • CRBN • IKZF1

Iberdomide plus daratumumab and dexamethasone (IberDd) in patients with newly diagnosed multiple myeloma by renal function: A subgroup analysis of the CC-220-MM-001 trial (ASH 2025) - P1/2 | "Introduction: Lenalidomide (LEN) plus daratumumab (DARA) and dexamethasone (DEX) is a standard-of-care treatment for transplant-ineligible (TNE) newly diagnosed multiple myeloma (NDMM). Despite the observed numerical differences in ORR and CR between RI subgroups, logisticregression analyses showed no correlation between baseline CrCl and key efficacy and safety endpoints,suggesting that RI does not impact clinical outcomes in pts with TNE NDMM treated with IberDd, and thatIBER dose modifications are not required for pts with mild to moderate RI. These data are consistent withprevious observations in pts with RRMM receiving IBER+DEX."

Clinical • Febrile Neutropenia • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Plasmacytoma • Renal Disease • CRBN • IKZF1

Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "IberCd is an all-oral and active combination for patients with relapsed and refractory multiple myeloma that showed clinically meaningful activity. This regimen offers a valuable treatment option for patients who have received two to four previous lines of therapy and compares favourably with other available treatments."

Journal • P2 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Targeted Protein Degradation • Venous Thromboembolism • CRBN

IKZF3 Promotes Gastric cancer Progression and Oxaliplatin Resistance via PI3K/AKT/mTOR Activation. (PubMed, J Gastroenterol Hepatol) - "IKZF3 drives GC progression and oxaliplatin resistance by activating PI3K/AKT/mTOR signaling. It is a potential prognostic biomarker and therapeutic target, supporting further development of LY294002 and Iberdomide for GC treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • IKZF3

Preclinical Optimization of T Cell Redirected Therapy (ICKSH 2026) - "In contrast, combining TCEs with the IMiD pomalidomide enhanced T cell activation and improved initial responses, even in IMiD -resistant tumors, indicating a tumor -extrinsic effect of Ikaros degraders on T cell fitness...Step -up TCE dosing with CELMoD (iberdomide or mezigdomide) plus dexamethasone pretreatment was well tolerated, reduced inflammatory cytokine production, lim ited T cell exhaustion, prevented Treg accumulation, and induced sustained complete responses with extended survival. As an alternative, combining TCEs with cyclophosphamide (Cy) enabled tumor debulking overcoming primary resistance , generated durable resp onses, and was curative in Cy- sensitive tumors...Intermittent TCE dosing preserved BCMA expression but allowed tumor -extrinsic resistance mechanisms currently under investigation . Together, these findings demonstrate that tumor burden is a dominant driver of primary TCE resistance, that controlled modulation of T cell activation is essential..."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • CD4 • IKZF1 • TIGIT • TNFRSF17

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1b/2a | N=464 | Recruiting | Sponsor: Celgene | Trial completion date: May 2027 ➔ Oct 2027

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

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=106 | Not yet recruiting | Sponsor: Celgene Corporation | Trial primary completion date: Aug 2018 ➔ Apr 2020

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

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=118 | Recruiting | Sponsor: Celgene | Trial primary completion date: Aug 2018 ➔ Jul 2020

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

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=106 | Recruiting | Sponsor: Celgene Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1b/2a | N=464 | Recruiting | Sponsor: Celgene | Trial completion date: Oct 2027 ➔ Feb 2028 | Trial primary completion date: Aug 2021 ➔ Apr 2022

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

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1b/2a | N=154 | Recruiting | Sponsor: Celgene | Phase classification: P1/2 ➔ P1b/2a | N=118 ➔ 154 | Trial completion date: May 2022 ➔ Jan 2023 | Trial primary completion date: Jul 2020 ➔ Mar 2021

Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=118 | Recruiting | Sponsor: Celgene | Trial primary completion date: Mar 2018 ➔ Aug 2018

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

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma (clinicaltrials.gov) - P1b/2a | N=449 | Recruiting | Sponsor: Celgene | Trial completion date: Feb 2028 ➔ Oct 2029

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