Innovent's Trispecific Antibody IBI3003 Advances Into Phase 3 for Relapsed or Refractory Multiple Myeloma

Innovent Biologics announced on June 21, 2026 that the first patient has been dosed in TriadicMM-1 (NCT07623798), a multicenter, randomized, controlled, open-label phase 3 clinical trial evaluating IBI3003 against investigator's choice of regimen — either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) — in adults with relapsed or refractory multiple myeloma (R/R MM) who have received between two and five prior lines of therapy.¹ The trial's primary endpoint is progression-free survival (PFS) assessed by an independent review committee.

Why does the multiple myeloma field need new agents?

Multiple myeloma is a clonal malignancy of plasma cells and the second most common hematologic cancer globally, with incidence continuing to rise alongside an aging population.² While the introduction of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has substantially improved outcomes over the past two decades, the disease remains largely incurable.² For patients who have experienced relapse after multiple prior lines of therapy, the treatment calculus becomes increasingly difficult.

"With each recurrence, symptoms reappear, quality of life declines, and both the likelihood and duration of treatment response typically decrease," noted Peng Liu, MD, of Zhongshan Hospital Affiliated to Fudan University, principal investigator of the TriadicMM-1 study. "There remains a significant and urgent unmet medical need for novel therapeutic agents targeting alternative mechanisms of action to better control the disease, achieve deeper and more durable responses, and improve long-term outcomes."¹

How does a trispecific antibody differ from current approaches?

Currently approved T-cell engagers in multiple myeloma are predominantly bispecific antibodies, each targeting a single myeloma antigen — either BCMA or GPRC5D — alongside CD3 on T cells. While response rates for these agents are meaningful in heavily pretreated patients, antigen escape — whereby myeloma cells downregulate or lose the targeted antigen — has emerged as a mechanism of resistance limiting their durability.³

IBI3003 was designed to address this vulnerability. Constructed on Innovent's proprietary Sanbody platform, IBI3003 simultaneously engages GPRC5D and BCMA on malignant plasma cells while binding CD3 on T cells, redirecting cytotoxic T-cell activity through two independent tumor-associated antigens.¹ In preclinical models, its antitumor activity was superior to marketed bispecific antibody benchmarks, and it showed particularly potent tumor killing in cell models with low expression of either BCMA or GPRC5D — conditions that can predict resistance to single-target agents.¹

The FDA granted IBI3003 fast track designation in January 2026 for the treatment of R/R MM in patients who have received four or more prior lines of therapy including at least a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.⁴ A phase 1/2 trial is currently underway in the US, Australia, and China (NCT06083207).

What does early clinical data show?

Data from the phase 1/2 study, presented at the American Society of Hematology Annual Meeting in December 2025, provided the efficacy and safety foundation for the phase 3 program. Among 24 patients treated at doses of 120 μg/kg or higher — the range selected for further development — the overall response rate was 83.3%, including four stringent complete responses, seven very good partial responses, and nine partial responses.¹ Notably, the ORR was 80% in patients with extramedullary disease and 77.8% in patients previously treated with BCMA- and/or GPRC5D-directed therapies, populations that typically have limited options.¹

Among patients who achieved complete response or better, the minimal residual disease (MRD) negativity rate was 100%, as assessed by validated next-generation sequencing at a threshold of 10⁻⁵.¹ These findings, while early and drawn from a small dataset, suggest IBI3003 may retain activity even in patients whose disease has progressed after prior bispecific or CAR-T therapy targeting the same antigens.

On safety, all cases of cytokine release syndrome (CRS) were Grade 1 or 2, and most treatment-emergent adverse events related to GPRC5D targeting — including effects on the oral cavity, skin, and nails — were Grade 1 to 2, with two patients experiencing Grade 3 rash.¹

What is the broader significance of this milestone?

IBI3003 is the second trispecific antibody globally to advance into pivotal phase 3 development in the R/R MM setting, reflecting a broader industry push to move beyond dual-target T-cell engagers toward constructs that may more durably engage myeloma cells across heterogeneous disease states.⁵ BioPharm International previously reported on IBI3003's FDA Fast Track Designation, noting that regulatory acceleration for trispecific antibodies in myeloma may influence their rapid progression toward commercialization.⁴

"IBI3003 monotherapy has demonstrated encouraging efficacy and a favorable safety profile in R/R MM patients who had received three or more prior lines of therapy," said Hui Zhou, MD, PhD, chief R&D officer, Oncology, at Innovent. "Looking ahead, Innovent will deepen its dual innovation in ADC and immunotherapy, and is committed to delivering cutting-edge therapies to patients worldwide."¹

References

1. Innovent Biologics announces first patient dosed in a Phase 3 clinical trial of IBI3003 (GPRC5D/BCMA/CD3 tri-specific antibody) for the treatment of multiple myeloma. (2026 Jun 21). Innovent Biologics. https://www.prnewswire.com/news-releases/innovent-biologics-announces-first-patient-dosed-in-a-phase-3-clinical-trial-of-ibi3003gprc5dbcmacd3-tri-specific-antibody-for-the-treatment-of-multiple-myeloma-302805881.html
2. Rajkumar SV. (2022 Aug). Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. https://pubmed.ncbi.nlm.nih.gov/35560063/
3. van de Donk NWCJ, O'Neill C, de Ruijter MEM, Verkleij CPM, Zweegman S. (2023 Nov 1). T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA. Curr Opin Oncol. https://pubmed.ncbi.nlm.nih.gov/37501530/
4. Mirasol F. (2026 Jan 28). FDA fast tracks Innovent's trispecific antibody for multiple myeloma. BioPharm International. https://www.biopharminternational.com/view/fda-fast-tracks-innovent-s-trispecific-antibody-for-multiple-myeloma
5. Schoenthaler E. (2026 May 26). Late-stage CAR-T, bispecific therapies drive transformation in the multiple myeloma pipeline. BioPharm International. https://www.biopharminternational.com/view/late-stage-car-t-bispecific-therapies-drive-transformation-in-the-multiple-myeloma-pipeline