FDA Grants Fast Track Designation to IBI3003 for R/R Multiple Myeloma

The FDA granted fast track designation (FTD) to IBI3003, a first-in-class trispecific antibody, for the treatment of patients with relapsed or refractory multiple myeloma (R/R MM) with progression after at least 4 prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody.¹

Despite the advent of chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, many patients eventually relapse due to antigen loss or treatment resistance. IBI3003 aims to address these limitations by simultaneously targeting 2 validated myeloma antigens, BCMA and GPRC5D, while engaging CD3 on T cells to facilitate tumor lysis.

“IBI3003 monotherapy has demonstrated encouraging efficacy and a favorable safety profile in R/R MM patients who had received 3 or more prior lines of therapy,” said Hui Zhou, PhD, chief research and development officer of Oncology at Innovent Biologics, in a news release. “Notably, meaningful clinical activity was observed even in high-risk patients with EMD [extramedullary disease] or those previously treated with anti-BCMA and/or GPRC5D-targeted therapies, highlighting IBI3003’s potential to address key unmet needs. Its overall manageable safety profile further supports continued investigation and the potential for durable survival benefit.”

Key Data from ASH 2025

The FDA’s decision was bolstered by clinical data presented at the American Society of Hematology (ASH) Annual Meeting in December 2025. A phase 1/2 study (NCT06083207) evaluated 39 patients in China and Australia with heavily pretreated R/R MM.

At a median follow-up of 3.25 months, patients who received at least 120 μg/kg (n=24), the overall response rate (ORR) was 83.3%, including 16.7% (n = 4) with stringent complete response, 29.1% (n = 7) with very good partial response, and 37.5% (n = 9) with partial response.^2,3 An ORR of 80% was achieved in patients with EMD, and the ORR was 77.8% among patients who had previously failed BCMA- or GPRC5D-directed therapies, suggesting IBI3003 can overcome resistance to existing T-cell–directed therapies.

All 4 patients who achieved a complete response or better were found to be minimal residual disease-negative at a threshold of 10^-5 via next-generation sequencing.

Safety and Tolerability Profile

Toxicity is a primary concern with T-cell engaging therapies, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). IBI3003 demonstrated a manageable safety profile. All reported cases of CRS (64.1%) were grade 1 or 2. Only 2 cases of grade 1 to 2 ICANS occurred (6.1%), with no high-grade neurotoxicity reported.

Dose-limiting toxicity was reported in 2 patients, who both experienced grade 4 platelet count decrease which later recovered. Common adverse events (AEs) associated with GPRC5D targeting including skin, nail, and oral cavity changes, were primarily grade 1 or 2, with only 2 instances of grade 3 rash. The most common AEs of grade 3 or higher were hematologic and mainly occurred during step-up dosing and were considered manageable and recoverable.

Phase 1/2 Study Design

The first-in-human study of the trispecific antibody enrolled patients who have failed at least 2 prior lines of treatment including an IMiD, PI, and anti-CD38 antibody. IBI3003 was given subcutaneously once weekly. Dose escalation ranged from 0.1 to 1500 μg/kg, and 1 to 3 priming doses were given. The median age of the patients was 62 years, 64.1% were classified as high risk by mSMART criteria, and 46.2% had EMD. At the time of data cutoff, the median duration of treatment was 12.14 weeks.^1,2

Next Steps After FTD

The FTD program is designed to expedite the development of drugs that fill unmet medical needs for serious conditions and enables more frequent communication with the FDA and eligibility for priority review.¹ In December 2025, IBI3003 received IND approval from the FDA, enabling initiation of a phase 1/2 clinical trial in the United States.

The phase 1/2 trial in China and Australia had limited duration of follow-up and investigators anticipated greater antitumor response over time as the dose-escalation and -expansion trial continues. With the new FTD and IND approval, a US-based trial can be initiated.

“The [FTD] 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,” added Zhou in the news release.

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/bdcsba7a

2. 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/y8rzj2sk

3. 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