Announcement • Jun 22
Innovent Biologics Doses First Patient In Phase 3 Clinical Trial Of IBI3003 For Multiple Myeloma
Innovent Biologics announced that the first patient has been dosed in the Chinese pivotal Phase 3 clinical trial (TriadicMM-1) of its self-developed innovative anti-GPRC5D, BCMA and CD3 tri-specific antibody IBI3003 for the second to fifth-line treatment of patients with relapsed or refractory multiple myeloma (R/R MM). IBI3003 is China's first self-developed anti-GPRC5D/BCMA/CD3 tri-specific antibody to enter the pivotal registrational Phase III clinical trial, aiming to bring a promising next-generation immunotherapy option for Chinese R/R MM patients. TriadicMM-1 (NCT07623798) is a multicenter, randomized, controlled, open-label Phase 3 clinical trial designed to evaluate the efficacy and safety of IBI3003 versus investigator's choice of regimen (pomalidomide, bortezomib and dexamethasone [PVd] or daratumumab, pomalidomide and dexamethasone [DPd]). The primary endpoint of the study is progression-free survival (PFS) assessed by the Independent Review Committee (IRC). Clinical data presented at the American Society of Hematology (ASH) Annual Meeting on December 7, 2025 demonstrated a tolerable safety profile and promising efficacy signals for IBI3003 in patients who had failed =2 prior lines of myeloma therapy: Thirty-nine patients with R/R MM who had previously received at least a PI, an IMiD, and an anti-CD38 monoclonal antibody were treated with IBI3003 at dose levels ranging from 0.1 µg/kg to 800 µg/kg and underwent at least one tumor assessment after baseline. As of the data cutoff date of 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). Among patients treated at doses =120 µg/kg (n=24), the overall response rate (ORR) was 83.3%, including 4 stringent complete responses (sCR), 7 very good partial responses (VGPR), and 9 partial responses (PR). In this cohort, the ORR was 80% among 10 patients with extramedullary disease (EMD) and 77.8% among 9 patients previously treated with BCMA- and/or GPRC5D-directed therapies. Among patients who achieved complete response or better, the minimal residual disease (MRD) negativity rate was 100% (n=4), as assessed by validated next-generation sequencing, with a threshold of 10-5, performed at a central laboratory. All cases of cytokine release syndrome (CRS) were Grade 1-2, with only 2 cases of Grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) reported. Most treatment-emergent adverse events (TEAEs) related to GPRC5D targeting, including those affecting the oral cavity, skin, and nails, were Grade 1–2, with two patients experiencing Grade 3 rash. Relevant dose optimization data (including RP2D selection) from this Phase 1/2 study will be presented at future academic conferences. In addition, IBI3003 has received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA) earlier this year. This designation applies to the treatment of R/R MM in patients who have received four or more lines of previous anti-myeloma therapies, that include at least a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. The Phase I/II clinical trial in the United States is currently underway. Multiple Myeloma is a malignant hematological malignancy originating from plasma cells in the bone marrow, ranking as the second most common blood cancer globally. Driven by an aging global population, the incidence of multiple myeloma is continuously rising. Although the introduction of innovative therapies—such as proteasome inhibitors, immunomodulatory drugs, and targeted agents—has significantly improved patient prognosis over the past decades, multiple myeloma remains largely incurable. For patients with relapsed/refractory multiple myeloma who have already progressed through 1-4 lines of therapy, subsequent treatment options become severely limited. With each successive line of therapy, the duration of remission shortens, and the prognosis worsens drastically. Consequently, there is a critical and unmet medical need for novel therapeutic regimens with superior efficacy, manageable safety profiles, and distinct mechanisms of action to overcome resistance, prolong overall survival, and preserve patient quality of life. IBI3003, constructed on Innovent's proprietary Sanbody® platform, is a novel trispecific antibody targeting G protein–coupled receptor, family C, group 5, member D (GPRC5D), B-cell maturation antigen (BCMA) and CD3. This molecular design aims to overcome single tumor antigen escape. Its antitumor activity in preclinical mouse models is superior to that of marketed bispecific antibody benchmarks, and it exhibits particularly potent tumor killing efficacy in vitro cell models with low expression of BCMA and GPRC5D. Currently, a Phase I/II clinical trial of IBI3003 is underway in China, Australia and U.S. (NCT06083207) to explore the safety, tolerability and efficacy of IBI3003 in subjects with R/R MM. In China, the program has advanced into pivotal registration stage with TriadicMM-1 (NCT07623798), a randomized, controlled, open-label Phase III study comparing IBI3003 to investigator's choice of regimens (DPd or PVd). The primary endpoint is progression-free survival (PFS) assessed by an independent review committee (IRC).
