Innovent's Trispecific Antibody IBI3003 Shows 83.3% Response Rate in Heavily Pretreated Multiple Myeloma Patients
核心洞察
Innovent Biologics (搜索) reported promising Phase 1 results for IBI3003, a novel trispecific antibody targeting GPRC5D (搜索), BCMA (搜索), and CD3 (搜索), achieving an 83.3% overall response rate in relapsed/refractory multiple myeloma patients at doses ≥120 μg/kg.
The therapy demonstrated efficacy in high-risk patient populations, including 80% response rate in patients with extramedullary disease and 77.8% in those previously treated with anti-BCMA (搜索) and/or anti-GPRC5D (搜索) therapies.
IBI3003 showed a manageable safety profile with cytokine release syndrome occurring in 64.1% of patients, all Grade 1-2, while achieving 100% minimal residual disease negativity in patients with complete response.
Innovent Biologics (搜索) has announced encouraging initial results from the first-in-human Phase 1 study of IBI3003, a novel trispecific antibody for relapsed or refractory multiple myeloma (R/R MM), presented at the 2025 American Society of Hematology (ASH) Annual Meeting. The therapy achieved an overall response rate (ORR) of 83.3% in patients treated with doses ≥120 μg/kg, demonstrating particular promise in high-risk patient populations who have exhausted standard treatment options.
Novel Trispecific Design Targets Multiple Escape Mechanisms
IBI3003 represents a unique approach to multiple myeloma treatment, simultaneously targeting GPRC5D (搜索), B-cell maturation antigen (BCMA (搜索)), and CD3 (搜索). This dual-targeting design against BCMA and GPRC5D aims to overcome single antigen escape mechanisms that limit the effectiveness of current therapies. In preclinical studies, IBI3003 exhibited superior in vivo anti-tumor activity compared to marketed benchmark bispecific antibodies in mouse models, with particularly prominent tumor-killing efficacy in cell models with low expression of BCMA and GPRC5D.
The Phase 1/2 clinical trial (NCT06083207) enrolled 39 patients across China and Australia with a median age of 62 years. These were heavily pretreated patients who had failed ≥2 lines of previous anti-myeloma therapies including at least a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. The median number of prior lines of therapy was 4, with 64.1% classified as high-risk per mSMART criteria and 46.2% having extramedullary disease.
Strong Efficacy Signals Despite Short Follow-up
Among the 24 patients treated with doses ≥120 μg/kg, the ORR reached 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). The median follow-up duration was 3.25 months, with a median treatment duration of 12.14 weeks.
Notably, IBI3003 demonstrated efficacy in challenging patient populations. Among patients with extramedullary disease treated at ≥120 μg/kg, the ORR was 80%. In patients who had previously received anti-BCMA (搜索) and/or anti-GPRC5D (搜索) therapies, the ORR was 77.8%. Among patients who achieved complete response or better, the minimal residual disease (MRD) negativity rate was 100%.
Manageable Safety Profile with Expected Toxicities
The safety profile proved manageable, with dose-limiting toxicity occurring in only 2 patients, both experiencing Grade 4 platelet count decrease that subsequently recovered. Treatment-emergent adverse events occurred in 97.4% of patients, with common events including cytokine release syndrome (CRS), neutrophil count decrease, anemia, and other hematological disorders.
CRS occurred in 64.1% of patients, while immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 6.1% of patients. Importantly, all CRS and ICANS events were Grade 1-2 and resolved with treatment. The study design included 1 to 3 priming doses to reduce CRS risk, and prophylactic use of tocilizumab may further reduce incidence, severity, and duration of CRS.
For GPRC5D (搜索) target-related adverse events involving the oral cavity, skin, and nails, no Grade ≥3 oral events were observed. Most skin and nail events were Grade 1-2, with only 2 patients experiencing Grade 3 rash.
Pharmacodynamic Evidence of Target Engagement
Biomarker analysis revealed that baseline soluble BCMA (搜索) (sBCMA) levels were high and variable in R/R MM patients, with a median level of 198 ng/mL (range: 10-3010 ng/mL). A profound and durable decline in serum sBCMA was observed across the 120, 360, and 540 μg/kg dose groups, demonstrating strong pharmacodynamic response and target engagement.
Addressing Critical Unmet Medical Need
Professor Peng Liu from Zhongshan Hospital Affiliated to Fudan University emphasized the urgent clinical need, stating that patients with R/R MM have poor prognosis after failing standard treatments, with an ORR of only 29.8%, median progression-free survival of 4.6 months, and median overall survival of 12.4 months. "The dual-target coverage of BCMA (搜索) and GPRC5D (搜索) by IBI3003 addresses the issues of antigen expression heterogeneity and treatment resistance associated with single-target drugs, reducing tumor escape," Liu noted.
IBI3003 is administered subcutaneously once weekly, with patients achieving partial response or better for ≥2 months after ≥6 months of continuous treatment eligible to switch to every-two-week maintenance dosing. The therapy is developed using Innovent's proprietary Sanbody platform and is designed to enable precise T-cell activation for tumor killing while improving safety through optimized CD3 (搜索) affinity.
The company continues dose optimization in the ongoing Phase 1 study, with expectations for deeper anti-tumor responses as follow-up duration extends and treatment continues.