As of July 19, 2021, 95 patients have received SC talquetamab. The RP2D was originally identified as a weekly SC dose of 405 µg/kg talquetamab with step-up doses. However, alternative dosing schedules that require less frequent administration continue to be investigated. A biweekly RP2D was also identified as an SC dose of 800 µg/kg talquetamab with step-up doses.

30 patients received the 405 µg/kg weekly dosing schedule (median age: 61.5 years [range 46–80]; 63% male; 100% triple-class exposed; 80% penta-drug exposed; 77% triple-class refractory, 20% penta-drug refractory; 30% prior BCMA-directed therapy; median follow-up: 7.5 mo [range 0.9–15.2]). 23 patients received the 800 µg/kg biweekly dosing schedule (median age: 60.0 years [range 47–84]; 48% male; 96% triple-class exposed; 70% penta-drug exposed; 65% triple-class refractory, 22% penta-drug refractory; 17% prior BCMA-directed therapy; median follow-up 3.7 mo [range 0.0–12.0]).

There were no treatment discontinuations due to AEs at either of the RP2Ds. The most common AEs at the 405 µg/kg weekly dose were CRS (73%; 1 patient had grade 3 CRS), neutropenia (67%; grade 3/4: 60%), and dysgeusia (60%; grade 2: 29%); skin-related AEs occurred in 77% (all grade 1/2; nail disorders: 30%) of patients, and infections occurred in 37% of patients (1 patient had grade 3 COVID-19 pneumonia). The most common AEs at the 800 µg/kg biweekly dose were CRS (78%; all grade 1/2), dry mouth (44%; all grade 1/2), and neutropenia (44%; grade 3/4: 35%); skin-related AEs occurred in 65% of patients (grade 3: 13%; nail disorders: 17%) and infections occurred in 13% of patients (1 patient had grade 3 pneumococcal sepsis).

In 30 response-evaluable patients treated with the 405 µg/kg weekly dose, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR] rate: 57%). In 17 response-evaluable patients treated with the 800 µg/kg biweekly dose, the ORR was 71% (≥VGPR rate: 53%). Responses were durable and deepened over time in both cohorts (Figure). Median duration of response (DOR) was not reached at either RP2D; the 6-month DOR rate for patients who received the 405 µg/kg weekly dose was 67% [95% CI: 41–84]. Serum trough levels of talquetamab were comparable at both RP2Ds. Consistent with the mechanism of action for talquetamab, pharmacodynamic data from cohorts treated at both dose levels showed peripheral T-cell activation and induction of cytokines.