Jeffrey Zonder, MD, discusses the efficacy results of a first-in-human trial of a bispecific monoclonal antibody in patients with relapsed/refractory multiple myeloma.
Jeffrey Zonder, MD, professor of hematology and oncology at the Karmanos Cancer Institute at Wayne State University, discusses the efficacy results of a first-in-human trial of a bispecific monoclonal antibody in patients with relapsed/refractory multiple myeloma, which were presented at the 2021 American Society of Hematology Annual Meeting and Exposition.
The phase 1/2 trial (NCT03761108) is designed to investigate the safety, tolerability, and dose-limiting toxicity of REGN5458, a BCMAxCD3 bispecific antibody, in patients with at least triple-refractory multiple myeloma. Patients received 16 weekly infusions of REGN5458 followed by infusions every 2 weeks until disease progression.
Objective response rate (ORR) as measured with the International Myeloma Working Group (IMWG) criteria is a secondary end point in the phase 1 portion and a primary end point in the phase 2 portion of the trial. Minimum residual disease (MRD) rate according to IMWG criteria was another secondary end point.
According to Zonder, REGN5458 had an impressive ORR that was comparable to approved agents even in the dose-finding phase, with an ORR in 51% in all patients. Of those who responded to treatment, 92.6% had a very good partial response (VGPR) and 48.1% had a complete response (CR) or stringent CR. At the 96 mg and 200 mg dose levels, the response rate was 73.3%. Zonder says it was 75% in those who received the highest dose levels of 200 mg to 800 mg.
Of the 10 patients who were tested for MRD, 4 had reached a status of undetectable MRD, according to Zonder.
The study is currently recruiting for the phase 2 portion to further assess ORR and other outcomes including overall survival and progression-free survival for up to 5 years.
0:08 | We saw early, deep, and durable responses with this bispecific antibody. The ORR for the whole study was 51%, which is impressive, because in a dose-finding study where you're starting at very low doses, you don't necessarily expect to see a particularly high response rate. Fifty-one percent compares pretty favorably to the products that are approved in the same space in multiple myeloma.
So it was 51% overall, [but] in the higher dose levels tested, the 200 to 800 mg dose levels, the ORR was 75%. The majority of those responses were pretty deep, with over half of patients achieving a VGPR or better. And that was actually also true—when you looked at responses across all dose levels, the rate of VGPR remained high, regardless of whether the response happened with low dose or at a higher dose. We saw CRs: 43% of the responses that we saw were CRs.
1:19 | There were a handful of patients that we did MRD testing on, which is ultra-sensitive testing, looking for extremely low levels of remaining disease. We had that data on 10 patients, and 4 patients actually achieved MRD negativity, which means we don't have a test that could detect the myeloma.