FDA Asked to Approve Talquetamab for Hard-to-treat Multiple Myeloma

Request supported by MonumenTAL-1 trial in relapsed or refractory patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Janssen has submitted an application with the U.S. Food and Drug Administration (FDA) asking that talquetamab be approved to treat relapsed or refractory multiple myeloma.

“We look forward to working closely with the FDA in their review of the talquetamab submission,” Peter Lebowitz, MD, PhD, global oncology therapeutic area head at Janssen Research and Development, said in a company press release.

Talquetamab is a bispecific antibody, meaning it binds to two targets simultaneously. Specifically, the antibody binds to GPRC5D, a receptor protein present at high levels on the surface of myeloma cells, but at lower levels in some healthy cells, and to the CD3 surface receptor protein on cancer-killing immune T-cells.

By targeting both GPRC5D and CD3, talquetamab is designed to direct the T-cells cells to destroy the cancer cells.

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Most relapsed or refractory multiple myeloma patients responded to treatment

Earlier this year, the FDA designated talquetamab a breakthrough therapy for relapsed or refractory multiple myeloma patients who previously received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

Talquetamab also received orphan drug designation in the U.S. and Europe for multiple myeloma, and a PRIority Medicines (PRIME) designation in Europe.

“Despite the therapies that have been developed for the treatment of multiple myeloma, there remains persistent unmet needs for patients who relapse or become refractory,” Lebowitz said.

Janssen’s application is supported by data from a Phase 1/2 clinical trial, called MonumenTAL-1, that is testing the therapy in people with relapsed or refractory multiple myeloma.

The trial’s Phase 1 portion (NCT03399799) determined two optimal dosing schedules for under-the-skin injections of talquetamab: 0.405 mg/kg, given once a week, and 0.8 mg/kg, administered every other week. These are being evaluated in the study’s Phase 2 portion (NCT04634552) among patients who have received at least three prior lines of therapy.

Latest data from the ongoing study were shared this month at the American Society of Hematology annual meeting, in the oral talk “Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1.”

As of May 16, 288 patients had been treated with talquetamab at one of the two recommended doses in Phase 1 or 2 of MonumenTAL-1. A total of 143 received the weekly regimen, while 145 were given the every-other-week regimen.

Patients’ median age was in the late 60s, their median time since diagnosis was nearly seven years, and they had received a median of five prior lines of treatment.

Combined patients’ data showed an overall response rate of about 73% — in other words, nearly three-quarters of these patients saw a reduction in cancer burden after treatment with talquetamab.

About 30% achieved a complete response (no detection of myeloma-specific markers) or better, and about 60% had a “very good partial response” or better, meaning the cancer burden was substantially reduced.

Bispecific antibody to direct the T-cells cells to destroy cancer cells

“This means that almost three-quarters of these patients are looking at a new lease on life,” Ajai Chari, MD, the study’s first author and the director of clinical research in the Multiple Myeloma Program at The Tisch Cancer Institute at Mount Sinai, said in a press release from Mount Sinai.

The median time to response was just over a month in both groups. In the weekly dosing group, the median duration of response to date is 9.3 months. Data on the response duration in those treated every other week are being collected, as well as for patients in both dosing groups who had a complete response or better.

Similar response rates were observed across several subgroups, with the exception of patients with a rare form of multiple myeloma that also extends to organs and soft tissues.

“Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients,” Chari said.

Adverse events were frequently reported among talquetamab-treated patients, though the majority were mild in severity.

Cytokine release syndrome — a potentially life-threatening complication of immunotherapy — occurred in about 3 out of every 4 patients. About two-thirds had skin-related side effects like rash, and around half reported changes in taste and/or nail disorders.

Infections occurred in about half of patients, and there were two deaths related to COVID-19 (one patient in each group).

About 5% to 6% of patients discontinued treatment due to adverse events, and dosing was reduced due to adverse events in about 1 out of every 10 patients.

The observed response rate with f is higher than that reported for most currently accessible therapies, Chari noted, suggesting it could offer a viable option for people with hard-to-treat multiple myeloma.

Talquetamab is also being evaluated in combination with other therapies in a number of clinical trials: RedirecTT-1 (NCT04586426), TRIMM-2 (NCT04108195), TRIMM-3 (NCT05338775), MonumenTAL-2 (NCT05050097), and MonumenTAL-3 (NCT05455320).