Innovent's trispecific antibody IBI3003 hits 84.6% ORR at 360 µg/kg in relapsed/refractory multiple myeloma
核心洞察
Innovent reported updated Phase 1 data for IBI3003, a trispecific antibody targeting GPRC5D (搜索), BCMA (搜索) and CD3 (搜索), in relapsed or refractory multiple myeloma (搜索) at the 2026 IMS Annual Meeting.
The recommended Phase 2 dose was set at 360 µg/kg, where 26 patients achieved an 84.6% overall response rate, including 11 stringent complete responses.
Responses were rapid, with a median time to first response of 0.99 months, and all centrally assessed complete responders were MRD negative.
Innovent Biologics (搜索) presented updated Phase 1 clinical data for IBI3003, a novel trispecific antibody targeting GPRC5D (搜索), BCMA (搜索) and CD3 (搜索), in patients with relapsed or refractory multiple myeloma (搜索) (R/R MM). The results were delivered in an oral presentation at the 23rd International Myeloma Society (IMS) Annual Meeting 2026.
Based on an integrated analysis of efficacy, safety and pharmacokinetic/pharmacodynamic data from dose optimization cohorts receiving 120, 360 and 540 µg/kg, the recommended Phase 2 dose (RP2D) was determined to be 360 µg/kg. At that dose, the company reported rapid, deep and durable response signals, particularly in heavily pretreated, high-risk patients with extramedullary disease.
Dose Optimization and Patient Population
The updated data came from the Phase 1 study NCT06083207, which enrolled patients with R/R MM who had failed at least two prior lines of therapy, including at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD) and one anti-CD38 (搜索)-based therapy, and who had relapsed or were refractory to their last anti-myeloma regimen. Patients with prior BCMA (搜索)- and/or GPRC5D (搜索)-targeted therapy were also eligible.
IBI3003 was administered subcutaneously once weekly (QW). Patients who received continuous treatment for at least 6 months and achieved a partial response (PR) or better for at least 2 months could switch to once-every-two-weeks (Q2W) dosing for maintenance. To reduce the risk of cytokine release syndrome (CRS), the study design incorporated 1 to 3 priming doses.
A total of 102 patients were enrolled in China and Australia, with doses ranging from 0.1 µg/kg to 800 µg/kg. The median patient age was 62 years (range 40-88), 37.1% were classified as high risk by mSMART criteria, and 53.9% had at least one site of extramedullary disease (EMD). Patients had received a median of four prior lines of therapy (range 2-12).
All patients had received at least three classes of therapy, including a PI, an IMiD and an anti-CD38 (搜索) antibody. Among them, 55.9% had received at least five classes of therapy, including at least two PIs, two IMiDs and one anti-CD38 antibody; 33.3% had previously received anti-BCMA (搜索) and/or anti-GPRC5D (搜索) therapies; and 88.2% were refractory to their last treatment. As of the June 30, 2026 data cutoff, median follow-up was 6.65 months (range 0.8-15.2).
Efficacy at the Recommended Phase 2 Dose
Twenty-six patients received IBI3003 at 360 µg/kg, with a median follow-up of 7.57 months. Median progression-free survival was not reached.
The overall response rate (ORR) was 84.6%, including 11 stringent complete responses (sCR), 4 very good partial responses (VGPR) and 7 partial responses. The ORR was 94.7% among 19 patients who had received 2 to 4 prior lines of therapy, 87.5% among 8 patients with non-bone-related EMD, and 92.3% among 13 patients without EMD.
Responses emerged quickly. Median time to first response was 0.99 months (range 0.9-8.3), median time to first response of at least VGPR was 1.87 months (range 0.9-4.6), and median time to first response of at least CR was 2.79 months (range 0.9-9.2).
Among patients who achieved CR or better as assessed by central laboratory next-generation sequencing, the minimal residual disease (MRD) negativity rate was 100% (n=8). Three patients achieved MRD negativity after only one treatment cycle.
Safety and Pharmacodynamics
Hematologic toxicities were the most common Grade 3 or higher treatment-related adverse events, occurring primarily during dose escalation and described as manageable and reversible.
CRS occurred in 52% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 3.9%. All events were Grade 1-2 and resolved with treatment. Prophylactic use of tocilizumab may reduce the risk of CRS, according to the company.
Infections occurred in 42.2% of patients, with Grade 3 or higher infections reported in 26.5%. For GPRC5D (搜索) target-related adverse events involving the oral cavity, skin and nails, no Grade 3 or higher oral events were observed. Most skin and nail events were Grade 1-2, with only two patients experiencing Grade 3 rash.
Biomarker analyses showed a significant and sustained decline in serum soluble BCMA (搜索) (sBCMA) levels across the 120 µg/kg, 360 µg/kg and 540 µg/kg dose groups. After three treatment cycles, the median reduction from baseline in sBCMA was 98.38% in the 360 µg/kg group.
Rationale for Dual Tumor-Antigen Targeting
IBI3003 was developed on Innovent's proprietary Sanbody platform. Its dual-targeting design against BCMA (搜索) and GPRC5D (搜索) is intended to overcome tumor escape caused by the loss or downregulation of a single tumor antigen. In preclinical mouse models, IBI3003 demonstrated superior in vivo anti-tumor activity compared with marketed benchmark bispecific antibodies targeting GPRC5D/CD3 (搜索) or BCMA/CD3, with prominent tumor-killing activity in in vitro cell models with low BCMA and GPRC5D expression.
Professor Peng Liu of Zhongshan Hospital Affiliated to Fudan University said patients with R/R MM have a poor prognosis after failing PIs, IMiDs and anti-CD38 (搜索)-based 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.
"Although bispecific antibodies are reshaping the treatment landscape of R/R MM, trispecific antibodies targeting two antigens simultaneously may help overcome treatment resistance caused by intra-tumor and inter-tumor heterogeneity, as well as treatment-induced antigen escape," Liu said. "A substantial unmet clinical need remains in R/R MM, particularly among heavily pretreated and high-risk patients."
Liu added that the dual-target coverage of BCMA (搜索) and GPRC5D (搜索) addresses antigen expression heterogeneity and treatment resistance associated with single-target therapies, reducing tumor escape, while optimized CD3 (搜索) affinity enables precise T-cell activation and tumor killing with improved safety. "In the Phase 1 results presented at this meeting, IBI3003 demonstrated a manageable safety profile and impressive efficacy at the 360 µg/kg dose, with an ORR of 84.6%," he said. "The ORR reached 94.7% among patients who had received 2 to 4 prior lines of therapy."
Ongoing Development Program
Phase 1/2 trials of IBI3003 (NCT06083207 and NCT07336472) are being conducted concurrently in China, Australia and the United States to evaluate safety, tolerability and preliminary efficacy in R/R MM.
In China, the program has advanced into a pivotal registrational stage. TriadicMM-1 (NCT07623798) is a multicenter, randomized, open-label Phase 3 study comparing IBI3003 with investigator's choice of therapy in patients with R/R MM who have received 1 to 4 prior lines of therapy. The primary endpoint is progression-free survival assessed by an independent review committee. A Phase 2 study of IBI3003 combined with a CD38 (搜索) monoclonal antibody for frontline multiple myeloma is also ongoing (NCT07764861).
Innovent stated that the efficacy and safety data support further evaluation of the clinical value of IBI3003 in the ongoing Phase 3 study.