BioPharma

Amgen’s bispecific antibody shows high response rate in multiple myeloma at ASCO

It remains unclear how many patients will relapse without the BCMA antigen, which would complicate their ability to use many CAR-T cell therapies later on. However, an expert said the drug's safety could be a challenge.

Amgen at ASCO 2019

A drug in development for the blood cancer multiple myeloma is showing strong early efficacy, but also a high rate of side effects that one expert said would likely present a challenge.

Phase I data presented Sunday at the American Society of Clinical Oncology meeting in Chicago for Thousand Oaks, California-based Amgen’s AMG 420 showed the drug produced responses in 13 of 42 patients across different dosing cohorts. Among 10 patients treated at the dose recommended for further development in the study, 400 micrograms per day, the overall response rate was 70 percent. Patients who received that dose accounted for five of the six patients who achieved a minimal residual disease-negative complete remission.

Serious side effects deemed related to treatment included two cases of peripheral polyneuropathy, a kind of nerve damage, and one case of edema. One patient also experience serious cytokine release syndrome. Infections were also common, occurring in 13 patients. Although two patients died during the study, the causes were not deemed to have been treatment-related.

AMG 420 is a bispecific T-cell engager or “BiTE” antibody that works by targeting myeloma cells via cell-surface antigens – in this case BCMA – and then using another antigen, CD3, to draw the body’s own T cells in to kill the cancer cells. It is similar to Blincyto (blinatumomab), a BiTE antibody that Amgen markets for acute lymphoblastic leukemia, targeting CD19 on the surface of cancer cells. Blincyto is also known to cause cytokine release syndrome, a constellation of immune reactions that results from rapid killing of cancer cells.

“What I saw told me we have a real signal,” said Dr. Paul Richardson, director of the multiple myeloma program at the Dana-Farber Cancer Institute in Boston, in an interview at ASCO following the presentation. “The challenge is going to be managing the safety profile because that’s really an issue.”

As a BCMA-targeting therapy, AMG 420 could be in a potential competitive position against CAR-T therapies in development that target the same antigen, such as bluebird bio and Celgene’s bb2121 and LCAR-B38M, from Johnson & Johnson’s Janssen subsidiary and Nanjing, China-based Legend Biotech. A potential advantage of AMG 420 is it’s off-the-shelf availability, meaning it would not require the cumbersome, complex manufacturing and logistical process that autologous CAR-Ts do.

“If CAR-T is difficult to deploy – and hopefully it’s not – Amgen has an advantage,” Richardson said. “Also it depends on cost, availability, of all those important things.”

However, the hope is that AMG 420 would be a part of the armamentarium rather than something to supplant CAR-T, Richardson said.

With that in mind, an important consideration is whether patients who relapse after treatment with AMG 420 still express the BCMA antigen, thus ensuring their eligibility for BCMA-directed CAR-T therapy later on. For Blincyto, Amgen has said about 10-15 percent of patients relapse as CD19-negative, and a leukemia expert interviewed at ASCO put the figure at 6 percent. The leukemia expert, the Moffitt Cancer Center’s Dr. Bijal Shah, added that about 42 percent of patients in a trial of a CD19-directed CAR-T therapy for acute lymphoblastic leukemia in adults had received prior Blincyto. However, it’s unclear what the situation is for AMG 420.

“Plasma cell infiltration was too low in patients with available data who relapsed while on AMG 420 to draw any conclusions regarding BCMA expression in this setting at the present time,” an emailed statement from Amgen read. “We will continue to evaluate this point in the ongoing Amgen-sponsored phase 1b/2 trial.”

Still, patients can still respond to BCMA-directed CAR-T therapies even if they test negative for BCMA, Richardson said. “There are patients who respond to CAR-Ts who are BCMA-negative,” he said. “Whether they do well is a different matter.”

Photo: Alaric DeArment, MedCity News

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