FDA Grants Fast Track Designation to IBI3003 in Relapsed/Refractory Multiple Myeloma

The FDA has granted fast track designation to the anti-GPRC5D/BCMA/CD3 tri-specific antibody IBI3003 for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 lines of anti-myeloma therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.¹

The drug is currently under evaluation in a phase 1/2 trial (NCT06083207) in patients with relapsed/refractory multiple myeloma whose disease had progressed on 2 or more prior lines of therapy. Results from the trial, which were presented at the 2025 ASH Annual Meeting and Exposition,² indicated that the agent produced an overall response rate (ORR) of 83.3% in patients who received at least a 120-μg/kg dose (n = 24), including 4 stringent complete responses, 7 very good partial responses, and 9 partial responses.¹

Moreover, the ORRs in this cohort of patients with extramedullary disease (n = 10) and those with prior exposure to BCMA- and/or GPRC5D-directed treatment (n = 9) were 80% and 77.8%, respectively.

The minimal residual disease–negativity rate was 100% (n = 4) in patients who achieved complete response or better per central assessment via next-generation sequencing, with a threshold of 10^–5.

“IBI3003 monotherapy has demonstrated encouraging efficacy and a favorable safety profile in patients [with relapsed/refractory multiple myeloma] who had received three or more prior lines of therapy. Notably, meaningful clinical activity was observed even in high-risk patients with [extramedullary disease] or those previously treated with anti-BCMA and/or GPRC5D-targeted therapies, highlighting IBI3003’s potential to address key unmet needs,” Hui Zhou, PhD, chief R&D officer of Oncology in Innovent, stated in a news release.

What is IBI3003?

IBI3003 is a tri-specific T-cell engager designed to inhibit GPRC5D and BCMA, thereby limiting tumor escape that can occur with single-antigen targeting. Preclinical data with IBI3003 have shown enhanced in vitro and in vivo antitumor activity compared with marketed benchmark T-cell engagers, including in cell lines and xenograft models that have low expression of BCMA and GPRC5D.

What was the design of the phase 1/2 trial?

Eligible patients received subcutaneous IBI3003 once weekly, with dose escalation from 0.1 to 1500 μg/kg.² Between 1 and 3 priming doses were given to reduce the likelihood of cytokine release syndrome (CRS). Adverse effects were graded per CTCAE v5.0. CRS and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines, and antitumor activity was assessed by 2016 International Myeloma Working Group criteria.

What other data have been shared for IBI3003?

As of the data cutoff date of November 7, 2025, 39 patients with relapsed/refractory multiple myeloma had received treatment with IBI3003 at dose levels ranging from 0.1 μg/kg to 800 μg/kg and undergone 1 or more post baseline tumor assessment.¹ The median follow-up was 3.25 months (range, 0.4-7.4), and the median duration of treatment was 12.14 weeks (range, 1.0-33.0).

With respect to safety, all cases of CRS were grade 1 or 2. The severity of ICANS was limited to grade 1 or 2 events, presenting in only 2 patients.

Most treatment-emergent adverse effects (TEAEs) were traced to GPRC5D targeting, including those affecting the oral cavity, skin, and nails, all of which were grade 1 or 2. Grade 3 rash also occurred in 2 patients.

What is the status of the agent’s development globally?

The phase 1/2 trial (NCT06083207) is ongoing in China and Australia. In December 2025, the FDA approved an investigational new drug application for IBI3003, allowing the launch of a phase 1/2 trial in the US.

What does this indication mean for the future of IBI3003?

“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,” Zhou concluded.

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. January 27, 2026. Accessed January 27, 2026. https://en.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=577
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