Talquetamab And Teclistamab Show Early Signal In Myeloma

Key Takeaways

• Responses were reported in most patients with extramedullary disease who received the dual bispecific regimen.
• Complete responses occurred in more than half of patients, and the reported objective response rate exceeded the approximately 61% seen in the earlier phase 1 readout.
• J&J presented simultaneous GPRC5D and BCMA targeting as a possible off-the-shelf strategy in a population with substantial unmet need.

Talquetamab plus teclistamab produced a 78.9% objective response rate in the 90-patient RedirecTT-1 phase 2 study of heavily pretreated multiple myeloma with extramedullary disease, presented at the European Haematology Association congress. Johnson & Johnson evaluated the dual bispecific regimen in a setting marked by advanced disease and extensive prior treatment exposure. The study evaluated a population with extramedullary disease, a setting in which prior studies have suggested patients have an 87% lower likelihood of responding to treatment than those without extramedullary disease.

RedirecTT-1 combined talquetamab, marketed as Talvey and directed against GPRC5D, with teclistamab, marketed as Tecvayli and directed against BCMA. Investigators treated patients with heavily pretreated multiple myeloma and extramedullary disease, where malignant plasma cells spread from the marrow to plasmacytomas elsewhere. The source noted that some participants had received as many as five earlier therapies before entering the phase 2 study. That prior treatment history also included previous exposure to BCMA-targeted CAR-T therapy in some cases. Overall, the population described in RedirecTT-1 reflected a substantial burden of earlier therapy and limited remaining treatment options.

More than half of treated patients achieved a complete response, with the reported rate reaching 54.4%. Researchers also compared the phase 2 findings with an earlier phase 1 readout that showed an objective response rate of about 61%. The comparison added context to the evolving signal for the two-drug regimen in this aggressive disease setting.

J&J said the findings endorsed the potential benefit of simultaneously targeting GPRC5D and BCMA and presented the combination as a possible off-the-shelf approach in this high-need clinical setting. The company also linked these data to JNJ-5322, a trispecific antibody designed to engage both targets within a single molecule. JNJ-5322 had also completed a phase 1 trial in heavily pretreated patients. That report cited objective response rates of 100% in patients untreated with BCMA- or GPRC5D-directed therapies and 86% overall. Talvey was described as the first approved GPRC5D-targeted therapy, while Tecvayli was the first approved BCMA-directed bispecific antibody.