SAN FRANCISCO and SUZHOU, China, Dec. 8, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major disease areas, announced the initial data of the first-in-human trial of IBI3003, a novel trispecific antibody targeting G protein-coupled receptor C5D (GPRC5D), B-cell maturation antigen (BCMA), and CD3 for the treatment of relapsed or refractory multiple myeloma (R/R MM), in an oral presentation at the 2025 American Society of Hematology (ASH) Annual Meeting. IBI3003 demonstrated favorable tolerability and a manageable safety profile. Despite the relatively short follow-up duration, IBI3003 has shown encouraging efficacy signals, particularly in high-risk patients with extramedullary disease (EMD) or those who have previously received anti-BCMA and/or anti-GPRC5D targeted therapies.
IBI3003 is a novel trispecific antibody targeting GPRC5D, BCMA and CD3 simultaneously. Its dual-targeting design against BCMA and GPRC5 aims to overcome single antigen escape in multiple myeloma (MM). In preclinical studies, IBI3003 exhibited superior in vivo anti-tumor activity over marketed benchmark bispecific antibodies in mouse models, with particularly prominent tumor-killing efficacy in in vitro cell models with low expression of BCMA and GPRC5D. Currently, Innovent is conducting a Phase 1/2 clinical trial (NCT06083207) of IBI3003 in China and Australia to evaluate its safety, tolerability, and efficacy in patients with R/R MM.
The first phase of the study enrolled eligible R/R MM patients who had failed ≥2 lines of previous anti-myeloma therapies that included at least a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 mAb; and must be relapsed or refractory to their last anti-myeloma regimen. Prior BCMA- or GPRC5D-targeting therapy was allowed.
IBI3003 was administered subcutaneously once weekly (QW). For patients who have received continuous treatment for ≥6 months and achieved partial response (PR) or better for ≥2 months could switch to Q2W as maintenance. To reduce the risk of cytokine release syndrome (CRS), 1 to 3 priming doses were included in the study design.
A total of 39 patients were enrolled in this phase in China and Australia, with a dose range of 0.1 μg/kg to 800 μg/kg. The median age of patients was 62 years (range: 40-79), 64.1% of whom were classified as high-risk per mSMART criteria, and 46.2% had ≥1 EMD. The median number of prior lines of therapy was 4 (range: 1-10). All patients had received at least three classes of drugs (PI, IMiD, and anti-CD38 antibody), 51.3% had received at least five classes of drugs (at least 2 PIs, 2 IMiDs, and 1 anti-CD38 antibody), 41% had previously received anti-BCMA and/or anti-GPRC5D therapies, and 76.9% were refractory to the last treatment. As of the data cutoff date, November 7, 2025, the median follow-up duration was 3.25 months (range: 0.4-7.4), and the median treatment duration was 12.14 weeks (range: 1.0-33.0).
Manageable Safety Profile of IBI3003 in R/R MM Patients
- Dose-limiting toxicity (DLT) only occurred in 2 patients, both of whom experienced Grade 4 platelet count decreased and recovered.
- 97.4% of patients experienced treatment-emergent adverse events (TEAEs). Common TEAEs included CRS, neutrophil count decrease, anemia, lymphocyte count decrease, white blood cell count decrease, and platelet count decrease.
- Hematological disorders were the most common Grade ≥3 TEAEs that mainly occurred during step-up dosing and were manageable and recoverable.
- The incidences of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were 64.1% and 6.1%, respectively, all of which were Grade 1-2 and resolved with treatment. Prophylactic use of tocilizumab may reduce incidence, severity, and duration CRS.
- The incidence of all-grade infections was 48.7%, with Grade ≥3 infections reported in 28.2% of patients.
- For GPRC5D target-related TEAEs involving the oral cavity, skin, and nails, no Grade ≥3 oral TEAEs were observed. Most skin and nail TEAEs were Grade 1-2, with only 2 patients experiencing Grade 3 rash.
Encouraging Efficacy and Depth of Response Observed with IBI3003 at Doses ≥120 μg/kg
- Encouraging efficacy was observed with a median follow-up of 3.25 months: Among patients treated with ≥120 μg/kg (n=24), the overall response rate (ORR) was 83.3%, including 4 cases of stringent complete response (sCR), 7 cases of very good partial response (VGPR), and 9 cases of partial response (PR).
- Among patients treated with ≥120 μg/kg, the ORR was 80% in 10 patients with EMD and 77.8% in 9 patients who had previously received anti-BCMA and/or anti-GPRC5D therapies.
- Among patients who achieved CR or better as assessed by central laboratory next-generation sequencing (NGS) testing, the minimal residual disease (MRD) negativity rate was 100% (n=4).
Potent and Sustained Pharmacodynamic Responses Observed with IBI3003 in R/R MM Patients
- Biomarker analysis showed that baseline soluble BCMA (sBCMA) levels were high and variable in R/R MM patients (median level: 198 ng/mL, range: 10-3010 ng/mL).
- A profound and durable decline in serum sBCMA across 120, 360 and 540 μg/kg groups was observed, demonstrating a strong pharmacodynamic response.
IBI3003 has demonstrated favorable tolerability and a manageable safety profile in R/R MM patients, with encouraging efficacy signals observed at doses ≥120 μg/kg. Efficacy responses were also observed in high-risk patients, including those with EMD or prior anti-BCMA and/or anti-GPRC5D therapies. Current follow-up remains relatively short, and deeper anti-tumor responses are expected with continued treatment and observation. Dose optimization for IBI3003 is ongoing in the Phase 1 study.
Professor Peng Liu, Zhongshan Hospital Affiliated to Fudan University, stated, "Patients with R/R MM have a poor prognosis after failing standard treatments, including PI, IMiD, and anti-CD38 therapies, with an ORR of only 29.8%, a median progression-free survival of 4.6 months, and a median overall survival of 12.4 months[1]. Therefore, there is an urgent unmet clinical need for these patients, particularly those with high-risk features such as EMD or prior anti-BCMA and/or anti-GPRC5D therapies. The dual-target coverage of BCMA and GPRC5D by IBI3003 addresses the issues of antigen expression heterogeneity and treatment resistance associated with single-target drugs, reducing tumor escape. Meanwhile, its optimized CD3 affinity enables precise T-cell activation for tumor killing while also improving safety. In the disclosed Phase 1 study results, IBI3003 showed a manageable safety profile and impressive efficacy data at doses ≥120 μg/kg, with an ORR of 83.3%. It also demonstrated significant efficacy in high-risk patients with EMD or prior anti-BCMA and/or anti-GPRC5D therapies, fully reflecting its potential in overcoming R/R MM. We look forward to the long-term follow-up survival data with continuous IBI3003 treatment."
About IBI3003 (Anti-GPRC5D/BCMA/CD3 Trispecific Antibody)
IBI3003 is a tri-specific TCE developed using Innovent's proprietary Sanbody platform to target both GPRC5D and BCMA. Designed to overcome drug resistance driven by single-antigen tumor escape, IBI3003 has exhibited superior in vivo antitumor activity in preclinical studies compared with marketed benchmark TCEs, especially in cell models with low BCMA and GPRC5D expression. Innovent is currently conducting a Phase 1/2 clinical trial (NCT06083207) of IBI3003 in China and Australia to evaluate its safety, tolerability, and efficacy in patients with R/R MM.
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 17 products in the market. It has 1 new drug applications under regulatory review, 4 assets in Phase 3 or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement:
(1) Innovent does not recommend the use of any unapproved drug (s)/indication (s).
(2) Ramucirumab (Cyramza®) and Selpercatinib (Retsevmo®) and Pirtobrutinib (Jaypirca®) were developed by Eli Lilly and Company.
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References
[1] Mateos M , Weisel K , Stefano V D ,et al.LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma[J].Leukemia, 2022, 36:1371 - 1376.DOI:10.1038/s41375-022-01531-2.
