Dr Burke on the Exciting Potential of Trispecific Antibodies

In this installment of Chief Insights in Oncology, John Burke, MD, of Rocky Mountain Cancer Centers in Denver, Colorado, and co-physician editor in chief, highlighted the exciting new results for a novel trispecific antibody called JNJ-5322, presented at recent summer meetings. This therapy is considered a trispecific antibody because it targets 3 different markers: CD3 on T cells and both BCMA and GPRC5D on plasma cells, essentially combining the targets of 2 different bispecific antibodies.

Bispecific antibodies have already revolutionized the treatment of hematological cancers, including multiple myeloma. Burke noted that 4 of these therapies are currently approved for myeloma, and he has found them to be both highly effective and well-tolerated by patients. The new trispecific antibody, JNJ-5322, seems to build on this success.

In the trial discussed, most patients had not received a prior bispecific antibody or CAR T-cell therapy. The results were remarkably effective, with an overall response rate of 100%. Furthermore, 70% of patients achieved a complete response, and 96% reached at least a very good partial response. This efficacy appears to be higher than that of other available therapies.

In terms of side effects, cytokine release syndrome (CRS) occurred in 69% of patients, but a prophylactic dose of tocilizumab (Actemra) was shown to reduce this rate to around 20%. The therapy also showed promising durability, with a 1-year progression-free survival rate of 74% across all doses and 95% at the recommended phase 2 dose.

Burke considers this report one of the most interesting in hematology from the recent meetings. He believes trispecific antibodies like JNJ-5322 could offer significant advantages, even over the already impressive bispecific antibodies. The investigators plan to initiate phase 2 and 3 trials in the near future.

Read Dr Burke's column from the September I 2025 issue of Targeted Therapies in Oncology.