TRIMM-2 phase Ib trial: Talquetamab + daratumumab in RRMM

Preclinical studies have shown that daratumumab in combination with talquetamab enhances multiple myeloma cell lysis. The phase Ib TRIMM-2 trial (NCT04108195), published by Chari et al. in Blood, assessed the safety and efficacy of talquetamab + daratumumab in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). Patients received talquetamab 0.4 mg/kg weekly (QW cohort; n = 14) or 0.8 mg/kg every other week (Q2W cohort; n = 51), as well as daratumumab 1,800 mg. The primary endpoint was safety.

Key data: The most frequently reported adverse events (AEs) were oral (89%), skin (80%), cytokine release syndrome (78%), and infections (71%). Grade 3–4 AEs occurred in 81.5% of patients, with 29% reporting infections. Two dose-limiting toxicities were observed in the Q2W cohort. At a median follow-up of 18.6 months, response rates were 71.4% and 82.4% in the QW and Q2W cohorts, respectively. The median progression-free survival (PFS) was 23.3 months in the QW cohort and 21.2 months in the Q2W cohort. Reduction of immunosuppressive regulatory T cells was observed in both cohorts. 

Key learning: Talquetamab + daratumumab demonstrated deep and durable responses with robust clinical activity and a manageable safety profile in heavily pretreated patients with RRMM. The promising efficacy and nonoverlapping safety profile further support talquetamab as a viable combination partner, and trials of talquetamab in combination with other antimyeloma agents, including IMiDs, anti-PD-1 monoclonal antibodies, and BCMA-targeting bispecific antibodies, are ongoing.