Iberdomide Hydrochloride

Results presented at IMS 2026 show ZENBEXUS in combination with daratumumab and dexamethasone doubled minimal residual disease-negative complete response rates versus daratumumab, bortezomib and dexamethasone (41.1% vs. 20.7%) Data reinforce the value of the ZENBEXUS-based triplet as an effective, easily administered treatment option for patients with relapsed or refractory multiple myeloma as early as first relapse Results simultaneously published in The Lancet Oncology Bristol Myers Squibb (NYSE: BMY) today announced first time presentation of results from the prespecified analysis of the pivotal Phase 3 EXCALIBER-RRMM trial (NCT04975997) evaluating ZENBEXUS™(iberdomide) in combination with daratumumab and dexamethasone (ZDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). At a median follow-up of 15.7 months in 420 evaluable patients, the study showed a statistically significant and clinically meaningful improvement in minimal residual disease (MRD)-negative complete response (CR) rate, with significantly more patients achieving an MRD-negative CR with ZDd compared to DVd (41.1% vs. 20.7% [95% CI: 11.5%–28.6%]; p<0.0001; odds ratio 2.75 [95% CI: 1.77–4.30]). The dual primary endpoints of the study are MRD-negative CR rate and progression-free survival (PFS). These data are being presented today in a late-breaking oral presentation [Abstract #LBA12] at the 23rd Annual Meeting of the International Myeloma Society (IMS 2026) taking place in Glasgow, Scotland (September 23–26, 2026). These data were also simultaneously published in The Lancet Oncology. Treatment benefit with ZDd was consistent across prespecified subgroups, including patients with prior lenalidomide exposure, and refractoriness to lenalidomide (including in the last prior line of treatment). The overall response rate (ORR) was 88.9% with ZDd compared to 76.1% with DVd, and the rate of complete response or better was also nearly doubled at 45.9% vs. 24.9%, respectively. “Achieving deep, MRD-negative complete responses early in relapse is strongly associated with long-term clinical benefit and overall disease control for patients with multiple myeloma,” said Sagar Lonial, MD, FACP, Professor and Chair of the Department of Hematology and Medical Oncology, Emory University School of Medicine, and Chief Medical Officer, Winship Cancer Institute of Emory University. “These detailed EXCALIBER-RRMM results demonstrate that adding oral iberdomide to this regimen doubled the rate of MRD-negative complete responses or better across subgroups compared to standard DVd, and delivered high rates of overall and complete responses, reinforcing the triplet as a highly effective and manageable regimen that can be easily administered across diverse care settings, including community practices.” The safety pro ZDd was consistent with what is expected of the combination. Grade 3/4 neutropenia occurred in 84.3% of patients treated with ZDd vs. 11.3% treated with DVd, occurring predominantly during the first two cycles. Neutropenia was mostly manageable with G-CSF support and temporary dose interruptions (dose reduction of ZENBEXUS due to neutropenia was 13.2%; discontinuation of ZENBEXUS due to neutropenia was 1.0%). Grade 3/4 infections occurred in 39.2% of patients treated with ZDd vs. 21.6% with DVd, with fatal infections remaining low (2.0% vs. 1.5%). Notably, rates of peripheral sensory neuropathy were markedly lower with ZDd compared with DVd (any grade: 12.3% vs. 42.6%; Grade 3/4: 2.9% vs. 5.4%). “These Phase 3 results reinforce the potential of ZENBEXUS to advance treatment for patients with relapsed or refractory multiple myeloma,” said Cristian Massacesi, executive vice president, chief medical officer and head of development, Bristol Myers Squibb. “As the first therapy in multiple myeloma to demonstrate superiority on an MRD-negative complete response primary endpoint, ZENBEXUS marks an important advance for patients and further validates the potential of targeted protein degradation to expand what is possible in multiple myeloma.” Based on these results from EXCALIBER-RRMM, ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone received accelerated approval from the U.S. Food and Drug Administration for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent on August 13th, marking the arrival of a new treatment class. Evaluation of the dual primary endpoint of PFS in the confirmatory analysis cohort (n=800) is ongoing. Bristol Myers Squibb extends its gratitude to the patients, families, and investigators involved in the EXCALIBER-RRMM clinical trial. EXCALIBER-RRMM (NCT04975997) is a Phase 3, multicenter, two-stage, randomized, open-label study evaluating the efficacy and safety of ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone (ZDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). The study included a dose optimization stage and was designed to assess dual-primary endpoints of minimal residual disease (MRD)-negative complete response (CR) rate and progression-free survival (PFS), with additional secondary endpoints including overall survival (OS), overall response rate (ORR), safety and sustained MRD negativity. Eligible participants included adults with 1 to 2 prior lines of anti-myeloma therapy with progressive disease. A total of 939 patients were randomized. The primary efficacy population for MRD-negative CR included the first 420 patients randomized to the ZENBEXUS (1 mg) + Dd arm (n=207) or the comparator daratumumab, bortezomib, and dexamethasone (DVd) arm (n=213). Treatment in both arms was administered until disease progression or unacceptable toxicity. Targeted protein degradation (TPD) is a differentiated research platform at Bristol Myers Squibb built on more than two decades of scientific expertise, providing new avenues to degrade therapeutically relevant proteins that were previously considered difficult to address. BMS is the only company that has successfully developed and commercialized protein degrader agents for the treatment of multiple myeloma. These agents, known as immunomodulatory drugs (IMiDs), helped establish the current standard of care in the treatment of this disease, which remains without a cure. BMS is building on this foundation with several investigational protein degraders in clinical trials, leveraging three different modalities including cereblon E3 ligase modulators (CELMoDs), ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs). This three-pronged approach enables matching the right therapeutic modality to a molecular mechanism of action to modulate targets most effectively and ultimately provides more opportunities for potential breakthroughs that may offer meaningful new options for patients across a broad range of diseases, in and beyond hematology and oncology. ZENBEXUS™ is also being evaluated in the EXCALIBER Maintenance study. At Bristol Myers Squibb, our mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. 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● 在2026年国际骨髓瘤研讨会（IMS 2026）上公布的研究结果显示，相比达雷妥尤单抗联合硼替佐米及地塞米松，iberdomide联合达雷妥尤单抗和地塞米松使微小残留病（MRD）阴性完全缓解率翻倍（41.1% vs. 20.7%） ● 数据进一步证实了基于iberdomide的三药联合方案是复发或难治性多发性骨髓瘤患者（早至首次复发）有效、给药便捷的治疗选择 ● 研究结果已同步发表于《柳叶刀·肿瘤学》 近日，百时美施贵宝首次公布了关键III期EXCALIBER-RRMM研究（NCT04975997）预设分析的结果。该研究旨在评估iberdomide联合达雷妥尤单抗和地塞米松（IberDd）对比达雷妥尤单抗联合硼替佐米及地塞米松（DVd）在复发或难治性多发性骨髓瘤（RRMM）患者中的疗效与安全性。在420例可评估患者中，中位随访15.7个月时，研究显示微小残留病（MRD）阴性完全缓解（CR）率取得了具有显著统计学意义和临床意义的改善：IberDd组达到MRD阴性CR的患者比例显著高于DVd组（41.1% vs. 20.7%［95% CI: 11.5%–28.6%］；p<0.0001；比值比2.75［95% CI: 1.77–4.30］）。研究的双主要终点为MRD阴性CR率和无进展生存期（PFS）。 上述数据已于2026年9月23日至26日在苏格兰格拉斯哥举行的第23届国际骨髓瘤学会年会（IMS 2026）上，作为突破性口头报告（摘要编号LBA12）发布，并同步发表于《柳叶刀·肿瘤学》。 在各预设亚组中，IberDd方案均显示出一致的的治疗获益，包括既往接受过来那度胺治疗的患者、以及对来那度胺耐药（包括上一线治疗期间对来那度胺耐药）的患者。IberDd组的总体缓解率（ORR）为88.9%，DVd组为76.1%；IberDd组达到完全缓解及以上的患者比例为45.9%，相比DVd组（24.9%）接近翻倍。 Sagar Lonial 博士 埃默里大学医学院 血液学与肿瘤内科学系教授兼系主任 埃默里大学温希普癌症研究所首席医学官 对于多发性骨髓瘤患者而言，在复发早期取得深度的MRD阴性完全缓解，与长期临床获益和整体疾病控制密切相关。 EXCALIBER-RRMM研究的详细结果表明，在治疗方案中使用口服iberdomide后，各亚组达到MRD阴性完全缓解及以上的比例为标准DVd方案的两倍，总体缓解率与完全缓解率亦表现优异。由此可见，该三联方案疗效确切，易于管理，适用于包括社区诊所在内的各类诊疗场景。 IberDd方案的安全性特征与该联合方案的预期安全性特征一致。3/4级中性粒细胞减少症在IberDd组和DVd组的发生率分别为84.3%和11.3%，且主要发生于前两个治疗周期。多数中性粒细胞减少症可通过粒细胞集落刺激因子（G-CSF）支持治疗及暂时中断给药得到有效管理（因中性粒细胞减少症导致iberdomide减量的比例为13.2%，导致终止iberdomide治疗的比例为1.0%）。3/4级感染在IberDd组和DVd组的发生率分别为39.2%和21.6%，致死性感染发生率均较低（2.0% vs. 1.5%）。值得注意的是，IberDd组外周感觉神经病变的发生率明显低于DVd组（任意级别：12.3% vs. 42.6%；3/4级：2.9% vs. 5.4%）。 Cristian Massacesi 百时美施贵宝执行副总裁 首席医学官兼研发负责人 此次III期研究结果进一步印证了iberdomide在复发或难治性多发性骨髓瘤治疗中的潜力。 作为首个在 MRD 阴性完全缓解这一主要终点上证实优效性的多发性骨髓瘤方案，iberdomide为患者带来了重要的治疗进展，也进一步验证了靶向蛋白降解技术在拓展多发性骨髓瘤治疗边界方面的巨大潜力。 基于EXCALIBER-RRMM研究的上述结果，iberdomide联合达雷妥尤单抗皮下注射液和地塞米松已于8月13日获得美国食品药品监督管理局（FDA）加速批准，用于治疗既往接受过至少一线治疗（包括一种蛋白酶体抑制剂和一种免疫调节剂）的多发性骨髓瘤成人患者，开创了全新的治疗品类。确证性分析队列（n=800）中双主要终点之一PFS的评估仍在进行中。 百时美施贵宝向参与EXCALIBER-RRMM临床试验的患者、家属和研究者致以衷心感谢。 说明 本资料中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。 Iberdomide尚未在中国获批。 关于EXCALIBER-RRMM 研究 （上下滑动阅读更多内容） EXCALIBER-RRMM（NCT04975997）是一项III期、多中心、两阶段、随机、开放标签研究，旨在评估iberdomide联合达雷妥尤单抗和地塞米松（IberDd）对比达雷妥尤单抗联合硼替佐米及地塞米松（DVd）在复发难治性多发性骨髓瘤（RRMM）患者中的疗效与安全性。研究包括剂量优化阶段，以微小残留病（MRD）阴性完全缓解（CR）率与无进展生存期（PFS）作为双主要终点，其他次要终点包括总生存期（OS）、客观缓解率（ORR）、安全性和持续MRD阴性。符合入组条件的患者为既往接受过1至2线抗骨髓瘤治疗且疾病处于进展期的成人患者。共有939例患者入组并随机分配。MRD阴性CR主要疗效分析人群纳入了前420例随机分配至iberdomide（1 mg）+Dd组（n=207）或达雷妥尤单抗、硼替佐米联合地塞米松组（n=213）的患者。两组患者均接受持续治疗，直至疾病进展或出现不可耐受的毒性。 关于靶向蛋白降解与CELMoD药物 靶向蛋白降解（TPD）是百时美施贵宝长期深耕的差异化研究平台，基于超过 20 年的科学探索，为降解传统意义上被认为“难以成药”但具有治疗价值的蛋白提供了全新路径。百时美施贵宝是目前唯一成功研发并商业化蛋白降解药物用于多发性骨髓瘤治疗的公司：旗下的免疫调节剂（IMiD®）帮助奠定了当前仍不可治愈的多发性骨髓瘤的治疗标准。在此基础上，百时美施贵宝正通过多个在研蛋白降解药物拓展这一平台，目前正在开展临床研究的三大治疗模态包括CELMoD药物、配体导向型降解剂（LDDs）和降解抗体偶联物（DACs）。这种“三管齐下”的研发方式，使百时美施贵宝能够将合适的治疗模态与特定的分子作用机制相匹配，从而最大程度地调控靶点，最终为血液疾病、肿瘤领域乃至更广泛疾病领域的患者提供更多潜在的突破性治疗选择。 关于在研试验 Iberdomide目前也正在EXCALIBER-Maintenance研究中接受评估。