golcadomide (CC-99282) / BMS - LARVOL DELTA

EPCORE NHL-5: A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=565 | Recruiting | Sponsor: Genmab | Phase classification: P1/2 ➔ P2

Adverse events • Phase classification • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CCND1 • CD20

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

GOLCADOMIDE ± RITUXIMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: UPDATED PHASE 1/2 RESULTS (ICML 2025) - P1/2 | "Responses were independent of cell of origin and tumor microenvironment status. These data support the ongoing development of GOLCA+R in pts with R/R NHL."

Clinical • IO biomarker • P1/2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRBN • IKZF1

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

TREATMENT OF NEWLY-DIAGNOSED FOLLICULAR LYMPHOMA WITH RITUXIMAB, GOLCADOMIDE +/- NIVOLUMAB- INTERIM ANALYSIS OF THE PHASE II TOP-FLOR STUDY (ICML 2025) - P2 | "Background: Standard rituximab (R) +lenalidomide (R2) or chemoimmunotherapy is effective in treatment-naïve follicular lymphoma (TN FL) but is associated with Grade 3–4 AE rates > 65% with elderly patients (pts) overrepresented...We have demonstrated immune augmentation, safety and efficacy of PD1/PDL1i nivolumab (N) +rituximab, and atezolizumab-obinutuzumab-radiotherapy in TN FL (Chong ASCO 2024; Barraclough Blood Adv 2025)... This is the first study to demonstrate that Rituximab-golcadomide +/-nivolumab is a highly effective combination therapy in TN FL with manageable toxicity, most commonly neutropenia and infection. Differences between arms could not be elucidated in this preplanned interim analysis. The study continues recruitment."

P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CRBN • PD-1

GOLSEEK-2: A PHASE 2 RANDOMIZED, OPEN-LABEL STUDY OF GOLCADOMIDE IN COMBINATION WITH RITUXIMAB IN PARTICIPANTS WITH NEWLY DIAGNOSED ADVANCED-STAGE FOLLICULAR LYMPHOMA (ICML 2025) - P2 | "The phase 1/2 study CC-99282-NHL-001 showed that GOLCA alone or in combination with R (GOLCA+R) was well tolerated, with promising activity in pts with heavily pretreated relapsed/refractory FL, including those with prior lenalidomide-based therapies and/or T-cell–directed therapies (Chavez et al., ASH 2024)... After a screening period of ≤ 5 weeks, approximately 90 pts with newly diagnosed advanced-stage FL will be randomized 1:1:1 to receive GOLCA+R 0.2 mg or 0.4 mg once daily from days 1–14 every 28 days in combination with R for 12 cycles or investigator's choice R-chemo (R-CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or R-bendamustine)...The primary endpoint is complete metabolic response during the GOLCA+R combination treatment period, assessed by the investigator and based on the Lugano 2014 response criteria. Secondary endpoints include overall response rate, duration of response, complete response rate at 30 months, progression-free..."

Clinical • Combination therapy • Metastases • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CRBN • IKZF1

GOLCADOMIDE, A CEREBLON E3 LIGASE MODULATOR (CELMoD) AGENT ± RITUXIMAB, IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: UPDATED PHASE 1/2 RESULTS (ICML 2025) - P1/2 | "As of 30 Dec 2024, 12 pts received GOLCA in Part A. 22 and 38 received 0.2 and 0.4 mg GOLCA+R in Part B; median (mdn; range) time from initial diagnosis was 59 months (mo) (10–420), mdn prior Tx lines was 3 (1–12; 28% had T-cell–directed Tx, 30% lenalidomide [len], and 30% were refractory to last Tx). With additional f/u, GOLCA continued to show promising efficacy with durable responses and no new safety signal in heavily pretreated pts with R/R FL, including pts with prior len and/or T-cell–directed Tx. GOLCA 0.4 mg +R will be evaluated in the Ph3 GOLSEEK-4 study as a fixed-duration, chemo-free, outpatient option in R/R FL."

Clinical • P1/2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CRBN • IKZF1

GOLSEEK-4: A MULTICENTER PHASE 3 RANDOMIZED OPEN-LABEL STUDY COMPARING EFFICACY AND SAFETY OF GOLCADOMIDE + RITUXIMAB VS INVESTIGATOR'S CHOICE IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (EHA 2025) - P3 | "Commonly used treatment regimens for relapsed/refractory (R/R) FL include non-cross-resistant chemoimmunotherapy or rituximab (R)-lenalidomide (len)...Approximately 400 pts with R/R FL will be randomized 1:1 between GOLCA+R or IC, consisting of R-len or R-chemotherapy (CHOP or bendamustine)... GOLSEEK-4 will evaluate the safety and efficacy of GOLCA+R as a fixed duration, chemotherapy-free, outpatient treatment for R/R FL patients who have received >1 line of systemic therapy."

Clinical • P3 data • Follicular Lymphoma • Hematological Malignancies • Immune Modulation • Immunology • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • CRBN • 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

GOLCADOMIDE (GOLCA), A CEREBLON E3 LIGASE MODULATOR (CELMOD™) AGENT ± RITUXIMAB (R), IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (R/R FL): UPDATED PHASE 1/2 STUDY RESULTS (EHA 2025) - P1/2 | "Primary objectives included safety and RP2D determination.As of 30 Dec 2024, 12 pts received GOLCA in Part A, and 22 and 38 received 0.2mg and 0.4mg GOLCA+R in Part B. In Part B, median time (range) from initial diagnosis was 59 mo (10-420), median prior Tx lines was 3 (1-12), 28% had prior T-cell-directed Tx, 30% had prior lenalidomide (len) and 30% were refractory to last Tx.In Part A, 4 pts completed 2 y of GOLCA, remaining in remission at last f/u; 8 discontinued (d/c) due to PD. With additional f/u, GOLCA continued to show promising efficacy with durable responses and no new safety signals. A higher ORR and similar tolerability were observed with GOLCA 0.4mg +R vs GOLCA and GOLCA 0.2mg +R, including in pts with prior len-based and/or T-cell-directed Tx. These data support continued development of GOLCA 0.4mg +R as a fixed-duration, chemo-free, outpatient option in R/R FL, to be evaluated in the Ph3 GOLSEEK-4 study."

Clinical • P1/2 data • Anemia • Febrile Neutropenia • Follicular Lymphoma • Immune Modulation • Immunology • Infectious Disease • Lymphoma • Neutropenia • Targeted Protein Degradation • CRBN • IKZF1

GOLCADOMIDE (GOLCA), A CEREBLON E3 LIGASE MODULATOR (CELMOD™) AGENT, ± RITUXIMAB (R) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): UPDATED PHASE 1/2 STUDY RESULTS (EHA 2025) - P1/2 | "With additional f/u, GOLCA+R continued to demonstrate a manageable safety profile with no new safety signals. Durable responses were shown in heavily pre-treated patients with R/R DLBCL. Responses were independent of cell of origin and tumor microenvironment status."

Clinical • IO biomarker • P1/2 data • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Targeted Protein Degradation • BCL2 • CRBN • IKZF1 • TP53

A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas (clinicaltrials.gov) - P1/2 | N=49 | Not yet recruiting | Sponsor: The Lymphoma Academic Research Organisation

New P1/2 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Based on the results of early studies…golcadomide is being evaluated in multiple phase 3 studies (Businesswire) - "GOLSEEK-1: golcadomide and R-CHOP chemotherapy vs. placebo and R-CHOP in patients with previously untreated high-risk LBCL (projected data in 2028); GOLSEEK-4: golcadomide and rituximab vs. investigator's choice in patients with R/R FL who received at least 1 prior systemic therapy (projected data in 2030)"

P3 data • Follicular Lymphoma • Large B Cell Lymphoma

Abstract #4160953: Updated results were presented from a study evaluating golcadomide with or without rituximab for the treatment of R/R follicular lymphoma (Businesswire) - P1/2 | N=438 | NCT03930953 | Sponsor: Celgene | "Patients with R/R FL who had received ≥2 prior lines of treatment received golcadomide monotherapy in the dose-escalation part of the study (Part A), followed by golcadomide once daily at 0.2 or 0.4 mg with or without rituximab in the expansion part (Part B). Results continued to show promising efficacy with durable responses in heavily pre-treated patients with R/R FL. In Part A, the ORR was 67%, with a complete response rate (CRR) of 42% for patients treated with golcadomide monotherapy. In Part B, the ORR was 94% and the CRR was 63% for patients treated with golcadomide 0.4mg + rituximab. The median DOR was 4.8 months at a median follow-up of 5.75 months. Responses were consistent in patients who received prior lenalidomide-based and/or T cell-redirecting therapy. The most common grade 3/4 treatment-related adverse events across dose levels in Part B (n=60) were neutropenia and anemia..."

P1/2 data • Follicular Lymphoma

EPCORE NHL-5: A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=565 | Recruiting | Sponsor: Genmab | Phase classification: P2 ➔ P1/2

Adverse events • Phase classification • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CCND1 • CD20

Golcadomide and Nivolumab in Patients With Non-Hodgkin Lymphoma With Refractory Disease After Chimeric Antigen T-cell Therapy (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: Natalie Galanina | Trial completion date: Jan 2028 ➔ Apr 2028 | Initiation date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial initiation date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Choice in Participants With Relapsed/Refractory Follicular Lymphoma (GOLSEEK-4) (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Celgene | Trial primary completion date: Jul 2030 ➔ Apr 2028

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

A Study to Assess the Safety, Tolerability, Efficacy, and Drug Levels of BMS-986369 (Golcadomide) in Participants With Relapsed or Refractory T-cell Lymphomas in Japan (GOLSEEK-3) (clinicaltrials.gov) - P1/2 | N=85 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Aug 2029 ➔ Oct 2030 | Trial primary completion date: Dec 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Golcadomide: Data readout from P3 GOLSEEK-4 trial (NCT06911502) for 2L+ follicular lymphoma in 2030 (Bristol-Myers Squibb) - Q1 2025 Results

P3 data • Follicular Lymphoma • Hematological Malignancies • Oncology

A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Choice in Participants With Relapsed/Refractory Follicular Lymphoma (GOLSEEK-4) (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Celgene

New P3 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Golcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy (clinicaltrials.gov) - P2 | N=41 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • BCL2

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: Feb 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2024 ➔ Jun 2027

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

Leveraging efficiency metrics for the optimization of CELMoDs™ as cereblon-based molecular glue degraders. (PubMed, RSC Med Chem) - "We applied these efficiency metrics retrospectively to track optimization of a clinical molecular glue degrader series, resulting in the identification of Golcadomide (CC-99282). This work illustrates that efficiency metrics are beneficial for the identification of molecular glue drug candidates."

Journal • Targeted Protein Degradation • CRBN

Golcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy (clinicaltrials.gov) - P2 | N=41 | Not yet recruiting | Sponsor: Mayo Clinic

New P2 trial • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • BCL2

FIL_RICCO: A Combination of Rituximab and CC-99282 As Front-line Therapy for Older Frail Patients with Diffuse Large B-cells Non-Hodgkin Lymphoma Evaluated with a Simplified Geriatric Assessment (sGA): a Phase II Study of the Fondazione Italiana Linfomi (FIL) (clinicaltrials.gov) - P2 | N=47 | Not yet recruiting | Sponsor: Fondazione Italiana Linfomi - ETS

New P2 trial • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology