Trispecific Antibody Earns FDA Fast Track Designation in Multiple Myeloma

The FDA has granted fast track designation to IBI3003, an investigational trispecific antibody, as a treatment for patients with relapsed/refractory multiple myeloma following at least 4 prior lines of treatment, according to a press release from the developer, Innovent Biologics, Inc.¹ Specifically, the designation pertains to patients who have received treatment including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.

Developers designed IBI3003 as a trispecific T-cell engager that targets GPRC5D, BCMA, and CD3. Investigators hypothesize that this molecule may mitigate tumor escape related to single-antigen targeting.

Investigators are currently evaluating IBI3003 among patients with relapsed/refractory multiple myeloma as part of a phase 1/2 trial (NCT06083207) in China and Australia, with plans to launch another phase 1/2 trial in the US. Data from the trial in China and Australia were shared at the 2025 American Society of Hematology Annual Meeting & Exposition (ASH).^2,3

Findings revealed that among 24 patients who received IBI3003 at a minimum of 120 μg/kg, the overall response rate was 83.3%, with 4 patients achieving a stringent complete response (sCR), 7 having a very good partial response (VGPR), and 9 experiencing a PR. Additionally, the ORR was 80% among 10 patients who presented with extramedullary disease (EMD) and 77.8% in 9 who received prior anti-BCMA and/or anti-GPRC5D treatment. All 4 patients (100%) who achieved a CR or better per central laboratory next-generation sequencing assessment had minimal residual disease (MRD) negativity.

Investigators noted dose-limiting toxicities (DLTs) in 2 patients, and 97.4% of the population had treatment-emergent adverse effects (TEAEs). The most common TEAEs included cytokine release syndrome (CRS), decreased neutrophil counts, anemia, decreased lymphocyte counts, decreased white blood cell counts, and decreased platelet counts. The rates of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were 64.1% and 6.1%, respectively, which all consisted of grade 1/2 events that resolved during treatment.

Infections of any grade and grade 3 or higher occurred in 48.7% and 28.2% of patients, respectively. There were no grade 3 or higher TEAEs related to targeting GPRC5D, and most skin- and nail-associated TEAEs were grade 1/2 aside from 2 patients with grade 3 rash.

“IBI3003 monotherapy has demonstrated encouraging efficacy and a favorable safety profile in [patients with relapsed/refractory multiple myeloma] who had received 3 or more prior lines of therapy. Notably, meaningful clinical activity was observed even in high-risk patients with EMD or those previously treated with anti-BCMA and/or GPRC5D-targeted therapies, highlighting IBI3003’s potential to address key unmet needs,” Hui Zhou, MD, PhD, chief Research & Development officer of Oncology at Innovent, stated in the press release.¹ “Its overall manageable safety profile further supports continued investigation and the potential for durable survival benefit. The fast track designation granted by the US FDA represents an important milestone in the global development of IBI3003, and we look forward to further evaluating its potential to benefit patients worldwide.”

In the first-in-human phase 1/2 trial, 39 patients in China and Australia were assigned to receive IBI3003 at doses ranging from 0.1 μg/kg to 800 μg/kg. Investigators administered the agent subcutaneously once every week; patients who received continuous treatment for at least 6 months and maintained a PR or better for at least 2 months were eligible to switch to maintenance dosing every 2 weeks.

The trial’s primary end point was AEs.⁴ DLTs represented a secondary end point. Patients 18 years and older with an initial diagnosis of multiple myeloma per International Myeloma Working Group criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months were eligible for enrollment on the study.

References

1. Innovent announces IBI3003 (GPRC5D/BCMA/CD3 trispecific antibody) receives fast track designation from the U.S. FDA for relapsed or refractory multiple myeloma. News release. Innovent Biologics, Inc. January 27, 2026. Accessed January 27, 2026. https://tinyurl.com/mtjcnpuv
2. Li J, Li Z, Li C, et al. Initial results of the first-in-human phase 1 study of IBI3003, a novel trispecific antibody targeting GPRC5D, BCMA and CD3, in patients with relapsed or refractory multiple myeloma. Blood. 2025;146(suppl 1):702. doi:10.1182/blood-2025-702
3. ASH 2025 oral presentation: Innovent Biologics announces initial results of the first-in-human phase 1 study of trispecific antibody IBI3003 in relapsed or refractory multiple myeloma. News release. Innovent Biologics, Inc. December 8, 2025. Accessed January 27, 2026. https://tinyurl.com/5dw3ch4s
4. A study of IBI3003 in subjects with relapsed or refractory multiple myeloma. ClinicalTrials.gov. Updated December 13, 2024. Accessed January 27, 2026. https://tinyurl.com/yt74bdhj