Dr Cohen on Phase 1 Efficacy Data for Cevostamab in R/R Myeloma

What these [data] show is maybe a slightly lower ORR in a heavily pretreated population [vs other later-line multiple myeloma trials] but still good efficacy, and these responses could be durable, especially since this was a fixed-duration therapy.

Adam D. Cohen, MD, a professor of medicine in hematology-oncology at the Hospital of the University of Pennsylvania and director of myeloma immunotherapy at the Abramson Cancer Center in Philadelphia, discussed efficacy data from a phase 1 trial (NCT03275103) evaluating the FcRH5 x CD3 bispecific antibody cevostamab (RG 6160) in patients with relapsed/refractory multiple myeloma.

The fixed-duration, first-in-class agent was evaluated in the phase 1 trial, with results published in Nature Medicine. At the recommended phase 2 dose and schedule (n = 167), comprising a 160-mg target dose given once every 3 weeks for up to 17 cycles, the objective response rate (ORR) was 44.3% (95% CI, 36.5%-52.1%), Cohen noted. He added that responses varied according to whether patients had received prior BCMA-directed therapy; among the patients treated at the 160-mg target-dose level, 57.5% had received a prior BCMA-targeted agent. In patients who were naive to BCMA-directed therapy (n = 71), the ORR was 60.6%, which Cohen said was somewhat in line with what was reported in the original registration studies of BCMA-directed agents.

The ORRs may appear lower than those seen with some of those agents in their initial registration studies, but this trial enrolled a more heavily pretreated population, which influenced responses to some degree, according to Cohen. Patients treated at the 160-mg target dose level had received a median of 6 prior lines of therapy, and across the overall study population (n = 324), 89.5% of patients were triple-class refractory.

The other key efficacy end point was duration of response (DOR), Cohen said. At the recommended phase 2 dose, the median DOR was 10.4 months (95% CI, 6.2-15.0), and this reached 19.7 months (95% CI, 10.0-36.4) in patients who were naive to prior BCMA-directed therapy. Cohen emphasized that although the ORR was slightly lower in this heavily pretreated population, the responses observed were durable, even with a fixed-duration regimen, with patients experiencing ongoing responses following the completion of 17 treatment cycles. Cohen noted that some of the longest responders have been in response as far out as 4 years.