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ORLANDO -- A novel bispecific antibody targeting CD3 and the B-cell maturation antigen demonstrated early, deep, and durable responses in heavily pretreated multiple myeloma, according to results from a .

Among 43 patients with relapsed or refractory disease, 65.1% responded to various dose levels of the investigational therapy (REGN5459), including complete or complete responses in 51.2%, reported Attaya Suvannasankha, MD, of the Indiana University Simon Cancer Center in Indianapolis.

Furthermore, in patients who received the highest doses, the overall response rate (ORR) was substantially higher, at 90.5%, with a 61.9% complete or stringent complete response rate.

"What's important, too, is that this response actually is durable, with a median duration of response not yet reached," Suvannasankha said during a press briefing at the American Association for Cancer Research annual meeting here. She added that the longest responses are ongoing at 26 months or more at the latest data cut-off, and the probability of patients maintaining a response at 12 months is projected to be 78.1%.

Suvannasankha also noted that the therapy's side-effect profile appears to be acceptable, and an advantage of REGN5459 is that it was designed to bind relatively loosely to CD3 on T cells, in order to reduce cytokine release syndrome (CRS).

Across all dose levels, CRS was reported in 53.5% of the patients, rising to 81.0% at the highest dose levels -- "an increased incidence of CRS, but not an increase in severity," Suvannasankha observed, adding that almost all events were grade 1, with the exception of a single grade 2 event.

"Dr. Suvannasankha has shown very nicely the importance of getting novel precision medicine agents from the basic science laboratories into clinical work, but it does have to be done in a very thoughtful, methodical fashion," commented Lisa Newman, MD, MPH, of Weill Cornell Medicine in New York City, who moderated the press briefing.

She noted that the patient population in the current study of REGN5459 included those at the highest risk of morbidity and mortality from their disease.

"I'm excited about [the investigators'] future efforts, which I'm sure will involve looking at the medication in larger numbers of patients, and perhaps in patients with earlier stages of multiple myeloma," said Newman.

For their trial, the researchers recruited 43 patients with multiple myeloma who were refractory to or relapsed following three or more prior lines of treatment. Patients had a median age of 67, with 40% age 70 or older; participants were split evenly between men and women.

Participants had a median of five prior systemic regimens, and 72.1% were exposed to five types of therapy. The vast majority (86.0%) were refractory to the last line of therapy, with 81.4% at least triple-refractory, 62.8% at least quad-refractory, and 20.0% at least penta-refractory.

In the phase I portion of the trial, patients were treated with full doses of REGN5459 ranging from 3 mg to 900 mg, with 480 mg selected as the recommended phase II dose. Twenty-one patients were treated at the highest doses (480 mg to 900 mg). The nine patients treated at dose levels of 120 mg to 240 mg had an ORR of 66.7%, while the 13 patients treated at the lowest dose levels (3 mg to 60 mg) had an ORR of 23.1%.

Among patients with a complete or stringent complete response and available minimal residual disease (MRD) data, 15 of 19 (79%) were MRD negative at the 10^-5 threshold.

Regarding safety, Suvannasankha reported one dose-limiting toxicity at the 900 mg dose level, with that patient experiencing grade 3 hypoxia.

Apart from CRS, common treatment-emergent adverse events (TEAEs) included cough, diarrhea, fatigue, and neutropenia (39.5% of patients for each); and anemia (34.9%). Seven (16.3%) patients discontinued treatment due to TEAEs.

Infections occurred in 62.8% of patients, the most common of which were urinary tract infections (18.6%), pneumonia (16.3%), sinusitis (16.3%), and upper respiratory tract infections (16.3%). Thirteen patients (30.2%) had grade 3/4 infections, with pneumonia (9.3%), COVID-19 (7.0%), and sepsis (7.0%), the most common.

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