FDA Approval Sought for Iberdomide Plus Daratumumab/Dexamethasone in R/R Multiple Myeloma

The FDA has accepted for review a new drug application (NDA) seeking the approval of iberdomide (CC-220) plus daratumumab (Darzalex) and dexamethasone (IberDd) in the treatment of patients with relapsed or refractory multiple myeloma.¹

The NDA is based on data from the phase 3 EXCALIBER-RRMM study (NCT04975997), in which IberDd led to a statistically significant improvement in minimal residual disease (MRD) negativity rates vs daratumumab, bortezomib (Velcade), and dexamethasone (DVd) in this patient population.² Findings from the planned interim analysis were released in September 2025. At the time, it was announced that the trial would continue without changes to evaluate the other dual primary end point of progression-free survival (PFS), overall survival, and safety of the regimen.

“The FDA’s acceptance of this application is a testament to the potential of iberdomide, in combination with anti-CD38 monoclonal antibodies, as a novel, potent, oral treatment option, with a manageable safety profile, for patients with multiple myeloma,” Cristian Massacesi, executive vice president and chief medical officer of Bristol Myers Squibb, stated in a news release.¹ “Furthermore, our filing for iberdomide based on the MRD end point, underscores our commitment to pioneering new ways of advancing life-saving therapies for patients living with cancer.”

The application was assigned a Prescription Drug User Fee Act date of August 17, 2026. The regulatory agency granted breakthrough therapy designation to iberdomide for this population based on these findings.

What is the design of the EXCALIBER-RRMM study of iberdomide in multiple myeloma?

The open-label, multicenter, global EXCALIBER-RRMM study includes patients with relapsed or refractory multiple myeloma who have previously received 1 to 2 lines of antimyeloma therapy.³ Those who are refractory to CD38-targeted antibody therapy or bortezomib are excluded.

The study is comprised of 2 stages. In the first stage of the research, the dose-optimization phase, patients are randomized 1:1:1:1 to receive 1 of 3 doses of iberdomide—1.0 mg (arm A1), 1.3 mg (arm A2), or 1.6 mg (arm A3)—plus Dd or to arm B, where they receive DVd. A dose level of iberdomide will be selected for continued assessment in stage 2 of the study. In the second stage, patients with be randomized 1:1 to receive IberDd as part of 28-day cycles or DVd as part of 21- or 28-day cycles. Stratification factors include number of previous lines of therapy received (1 vs 2), age (≤ 70 years vs > 70 years), and International Staging System at study entry (I or II vs III).

The dual primary end points of the study are the efficacy in terms of MRD negativity at any time or in patients achieving a complete response (CR) or better, as well as PFS.

What additional data have read out with iberdomide in multiple myeloma?

Data from the phase 1/2 CC-220-MM-001 trial (NCT02773030) shared during the 22nd Annual International Myeloma Society Meeting and Expositionshowed that IberDd (n = 75) elicited an overall response rate (ORR) of 94.7%, which included a CR or better rate of 68.0%, in patients with transplant-ineligible/deferred newly diagnosed multiple myeloma.⁴ Moreover, the MRD negativity rate at a threshold of 10^-5 was 64.0%, and 56.0% of patients achieved MRD negativity with at least a CR.

In an exclusive interview with OncLive®,⁵Sagar Lonial, MD, FACP, FASCO,⁶ said: “CELMoDs are oral, so they’re easy to administer. “The toxicities are predominantly hematologic, something that those of us who take care of patients with myeloma are relatively comfortable... Having agents that are better tolerated than the immunomodulatory drug [IMiD] class is a huge step forward for patients. Perhaps [they will not require] the continuous maintenance approach that we’ve needed with IMiDs because they’re not as potent as CELMoDs. [With CELMoDs], we may be able to give limited duration therapy, get more efficacy, better safety, and, ultimately, talk about discontinuation.” Lonial is a professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as chief medical officer at Winship Cancer Institute of Emory University in Atlanta, Georgia.

Moreover, findings from cohort 2 of the phase 2 GEM-IBERDARAX trial (NCT05527340) that were also shared during the meeting indicated that IberDd elicited an ORR of 93.1% in evaluable patients with transplant-ineligible newly diagnosed multiple myeloma (n = 73) at a median follow-up of 11.1 months (range, 3.5-29.2).⁷ Responses were noted to deepen over time, with ORRs of 71.2%, 83.6%, 89.0%, 90.4%, 90.4%, and 91.8% during cycles 1 to 6 of therapy.

Previously, findings from part 1 of the phase 1b MagnetisMM-30 trial (NCT06215118) were presented during the 2025 ASH Annual Meeting and showed that when iberdomide was paired with elranatamab-bcmm (Elrexfio), it elicited an ORR of 95.5% (95% CI, 77.2%-99.9%) in evaluable patients with relapsed/refractory multiple myeloma (n = 22) at a median follow-up of 7.8 months (range, 0.7-11.3).⁸

References

1. US Food and Drug Administration accepts Bristol Myers Squibb’s new drug application for iberdomide in patients with relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. February 17, 2026. Accessed February 17, 2026. https://news.bms.com/news/corporate-financial/2026/U-S--Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-New-Drug-Application-for-Iberdomide-in-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx
2. Bristol Myers Squibb announces phase 3 EXCALIBER-RRMM study evaluating iberdomide in combination with standard therapies demonstrated a significant improvement in minimal residual disease negativity rates in relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. September 23, 2025. Accessed February 17, 2026. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Phase-3-EXCALIBER-RRMM-Study-Evaluating-Iberdomide-in-Combination-with-Standard-Therapies-Demonstrated-a-Significant-Improvement-in-Minimal-Residual-Disease-Negativity-Rates-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx
3. Lonial S, Dimopoulos MA, Berdeja JG, et al. EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma. Future Oncol. 2025;21(14):1761-1769. doi:10.1080/14796694.2025.2501920
4. Balari AS, Khan A, Oriol A, et al. Iberdomide, daratumumab, and dexamethasone (IberDd) in transplant-ineligible/deferred (TNE) newly diagnosed multiple myeloma (NDMM): updated results from the CC-220-MM-001 trial. Presented at: 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract OA-50.
5. Doherty K. Iberdomide plus daratumumab/dexamethasone displays high response rates in NDMM: Q&A with Sagar Lonial, MD, FACP, FASCO. OncLive.com. January 26, 2026. Accessed February 17, 2026. https://www.onclive.com/view/iberdomide-plus-daratumumab-dexamethasone-displays-high-response-rates-in-ndmm
6. Lonial S. Dr Lonial on data for iberdomide plus daratumumab/dexamethasone in newly diagnosed multiple myeloma. OncLive.com. February 5, 2026. Accessed February 17, 2026. https://www.onclive.com/view/dr-lonial-on-data-for-iberdomide-plus-daratumumab-dexamethasone-in-newly-diagnosed-myeloma
7. González-Calle V, Rosiñol L, Puig N, et al. Efficacy and safety of iberdomide, daratumumab, and dexamethasone, in transplant-ineligible NDMM patients: initial analysis of the GEM-IBERDARAX trial. Clin Lymphoma Myeloma Leuk. 2025;25(2):S363-S364. doi:10.1016/S2152-2650(25)04006-6
8. Suvannasankha A, Kaufman JL, Badros A, et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: results from the phase 1b MagentisMM-30 trial. Presented at: 2025 ASH Annual Meeting; December 6-9, 2025; Orlando, FL. Abstract #100.