Synergy of Bispecific Antibody and Immune Checkpoint Inhibitor

Janssen, a subsidiary of Johnson & Johnson (JNJ), presented data from the TRIMM-3 Phase 1b clinical trial at the 2025 European Hematology Association (EHA) meeting. The trial evaluated the combination of talquetamab (Talvey), a bispecific antibody, or teclistamab (Tecvayli), another bispecific antibody, with cetrelimab, a PD-1 inhibitor, in patients with relapsed/refractory multiple myeloma (RRMM). This trial goes beyond simply confirming drug safety; it strategically combines an immune checkpoint inhibitor to overcome the limitations of bispecific antibodies that re-engage T cells, aiming to maximize the synergistic effect of combination therapy. The goal was to demonstrate a mechanism that maintains a stronger immune response within the patient's body for a longer duration by preventing T-cell exhaustion, which can occur after bispecific antibody treatment.

Strong Efficacy Confirmed in the Talquetamab Combination Cohort

The clinical results showed that the talquetamab and cetrelimab combination arm (total of 44 patients, median follow-up of 11.5 months) achieved an overall response rate (ORR) of 70.5%, a very encouraging result. Notably, even in this patient population, which is known to be difficult to treat, a very good partial response (VGPR) or better was observed in 65.9% of patients, and a complete response (CR) was observed in 6.8%. The most noteworthy aspect of these results is that the median duration of response (DOR) was 16.8 months, and the DOR maintenance rate at 9 months was 72.6%, demonstrating excellent treatment durability. This suggests that the combination therapy can be a viable alternative for patients who have failed previous treatments, as it achieved an ORR of 68% in 19 high-risk patients who had previously been exposed to CD3-targeted T-cell redirection therapy.

Safety Profile Controlled to a Level Comparable to Monotherapy

One of the biggest concerns when combining immunotherapy and immune checkpoint inhibitors is the potential for a significant increase in immune-related adverse events. However, this trial demonstrated excellent tolerability. The observed adverse events (AEs) were generally similar to the safety profile observed with talquetamab monotherapy, and no additional toxicities were identified. The most common hematological adverse events were anemia and neutropenia, which are manageable with existing treatments, and the rate of Grade 3/4 severe infections was not significantly different compared to the monotherapy group. As a result, Johnson & Johnson (JNJ) has obtained important safety data demonstrating that multi-target combination therapy can elicit immune activation without posing a critical safety threat to patients.

A New Game-Changer in the Multiple Myeloma Market

The global multiple myeloma treatment market is projected to reach $31.0 billion by 2026, and the standard of care is currently shifting from daratumumab (Daratumumab, Darzalex)-based therapies to bispecific antibodies and CAR-T cell therapies. Johnson & Johnson (JNJ) already has a blockbuster drug, Darzalex, with annual sales of $10 billion, but it faces the challenge of fending off competition from BCMA-targeted drugs such as Elrexfio from Pfizer (PFE). The TRIMM-3 combination trial presented this time is expected to be a powerful weapon that will further solidify Janssen's oncology portfolio by including patients who are resistant to existing standard therapies.