Dr Cohen on Future Research Avenues for Cevostamab in R/R Myeloma

By switching the antigen target [after CAR T-cell therapy], you may be able to eliminate some of that BCMA-low or BCMA-negative reservoir of myeloma that could escape the CAR T cells and perhaps lead to deeper, more durable remissions.

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 ongoing and future avenues of investigation for the FcRH5 x CD3 bispecific antibody cevostamab (BFCR4350A; RG 6160) in relapsed/refractory multiple myeloma, spanning alternative routes of administration, novel combinations, and consolidation approaches after BCMA-directed CAR T-cell therapy.

As monotherapy in the phase 1 GO39775 study (NCT03275103), where fixed-duration treatment with the agent was evaluated in heavily pretreated patients with relapsed/refractory multiple myeloma, data showed an objective response rate of 44.3% at the recommended phase 2 dose of 160 mg given once every 3 weeks for up to 17 cycles (n = 167). Patients also experienced a median duration of response of 10.4 months (95% CI, 6.2-15.0) at this dose, and durable remissions were maintained following the completion of treatment, according to data published in Nature Medicine. Building on that activity, several efforts are now underway to extend the evaluation of the novel drug, Cohen said.

One line of development is a subcutaneous formulation of cevostamab, Cohen noted. Preliminary data presented at the 2025 ASH Annual Meeting and Exposition showed efficacy that was similar to that of the intravenous formulation, he said, which could offer patients added convenience going forward.

The agent is also advancing in combination regimens in a somewhat less heavily pretreated population, Cohen explained, with the phase 3 registrational CEVOLUTION trial (NCT07555938) now accruing patients. The worldwide study is comparing cevostamab plus pomalidomide (Pomalyst) and dexamethasone vs physician’s choice of standard-of-care regimens in patients who have received 1 to 3 prior lines of therapy, and it may serve as a path toward regulatory approval for cevostamab, he added.

Beyond CEVOLUTION, cevostamab is being explored in additional settings, Cohen said. An investigator-initiated phase 2 study (NCT05801939) at the University of Pennsylvania is evaluating cevostamab as consolidation following BCMA-directed CAR T-cell therapy, with treatment beginning approximately 2.5 to 3 months after CAR T-cell infusion. Cohen explained that switching the antigen target with cevostamab could help clear the BCMA-low or BCMA-negative reservoir of myeloma cells that may otherwise escape CAR T cells, potentially yielding deeper and more durable remissions. Collectively, these approaches represent the next steps in defining the role of cevostamab across the relapsed/refractory multiple myeloma treatment landscape, he concluded.