Johnson & Johnson Initiates Phase 1 Trial of JNJ-79635322, a Trispecific Antibody for Multiple Myeloma.
Next-Generation Trispecific Antibody Enters Clinical Trials
Johnson & Johnson's subsidiary, Janssen, has commenced a Phase 1 clinical trial (NCT06768489) of JNJ-79635322 (ramantamig), an innovative drug candidate for the treatment of multiple myeloma. This study will evaluate JNJ-79635322 in combination with daratumumab (Daratumumab, brand name Darzalex), a CD38-targeting antibody, in patients who are refractory to or have relapsed after prior standard therapies. Multiple myeloma is a hematologic cancer characterized by the abnormal proliferation of plasma cells, and it is often complicated by the development of resistance to treatments. Janssen aims to overcome the limitations of existing therapies and provide a new treatment option for relapsed patients through this combination therapy.
Synergistic Effects of Dual Targeting and T-Cell Activation
JNJ-79635322 is the first trispecific antibody designed to simultaneously target two key antigens on cancer cells, B-cell maturation antigen (BCMA) and G-protein coupled receptor class C group 5 member D (GPRC5D), while also binding to the CD3 receptor on immune T cells. This unique design effectively addresses the issue of antigen escape, which can occur due to the heterogeneity of cancer cells. By overcoming the resistance mechanisms of conventional dual-antibody therapies that target only a single antigen, JNJ-79635322 has garnered significant attention from both the academic and industrial communities. With its potent anti-tumor activity and precise targeting capabilities, it has the potential to become a leading agent in the next generation of immuno-oncology therapies.
Combination Design for Optimal Synergy
The clinical trial is designed with dose escalation and dose expansion phases to determine the optimal recommended Phase 2 dose (RP2D). Researchers have designed various combination regimens, including the addition of immunomodulatory drugs (IMiDs) such as lenalidomide or pomalidomide to the JNJ-79635322 and daratumumab combination. These IMiDs enhance the binding of immune cells to cancer cells and improve the tumor microenvironment. By creating a multi-faceted synergy of potent target cell killing and immune activation, the combination therapy is expected to improve overall survival and significantly extend progression-free survival (PFS).
Strengthening Market Dominance and Establishing a Future Standard of Care
Johnson & Johnson is actively conducting various combination trials to maintain the market dominance of Darzalex, a global blockbuster drug with annual sales of $14.351 billion (as of 2025). As the patent for Darzalex approaches expiration, securing successful combination data with the new drug candidate JNJ-79635322 is a key strategy to extend the patent protection and facilitate a natural transition to a new pipeline. If this Phase 1 trial demonstrates favorable safety and efficacy, it could proactively reshape the treatment paradigm for multiple myeloma. This is expected to widen the gap with competitors and solidify J&J's position in the multi-billion dollar market for hematologic malignancies.
The entry of JNJ-79635322 into Phase 1 clinical trials represents a key driver for reshaping the global multiple myeloma treatment market, which is projected to be worth approximately $25.88 billion by 2026. In the short term, it aims to extend the market life of Darzalex, which currently generates annual sales of $14.351 billion. In the long term, it seeks to diversify the portfolio by providing an alternative to overcome resistance to existing dual-antibody therapies such as Tecvayli and Talvey. In particular, its unique mechanism of action as the first trispecific antibody that simultaneously targets BCMA and GPRC5D will be a source of technological advantage for Janssen in the hematologic malignancy market. This will help prevent recurrence due to antigen loss in cancer cells, improve long-term patient survival, and maximize the long-term pipeline value of J&J if the clinical trial is successful.
Source: ClinicalTrials.gov (api_ct)