A bispecific antibody therapy was recently announced to be successful in as many as 73% of patients. The announcement was made at the American Society of Hematology (ASH) meeting—being held this week in New Orleans—a conference known for announcements of cancer clinical trial results.

Talquetamab, a bispecific antibody therapy, binds to both T cells and multiple myeloma cells—like “bringing your army right to the enemy.” The bispecific antibody (against CD3 and GPRC5D) redirects T cells to mediate killing of GPRC5D-expressing myeloma cells. The target—G protein–coupled receptor, family C, group 5, member D (GPRC5D), an orphan receptor expressed in malignant plasma cells—is different than the receptor used by other approved therapies­­.

Talquetamab was tested in Phase I and Phase II trials. The success of the off-the-shelf immunotherapy was seen even in patients whose cancer was resistant to all approved multiple myeloma therapies

The results of the Phase I trial were reported in The New England Journal of Medicine (NEJM), in the paper, “Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.” The Phase I trial established two recommended doses that were tested in the Phase II trial. The results of the Phase II trial were the data reported at the ASH meeting on Saturday morning. Both trials were sponsored and funded by Janssen.

The study participants had all been previously treated with at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.

“This means that almost three-quarters of these patients are looking at a new lease on life,” said Ajai Chari, MD, director of clinical research in the multiple myeloma program at the Tisch Cancer Institute at the Mt. Sinai Hospital in New York City. “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.”

Nearly all patients with myeloma who receive standard therapies continually relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatments are urgently needed. This study, while an early-phase trial designed to detect tolerability and find a safe dose, is an important step in meeting that need.

This Phase I clinical trial enrolled 232 patients at several cancer centers across the world between January 2018 and November 2021. Patients received a variety of doses of the therapy either intravenously or injected under their skin; future studies will focus on doses only administered under the skin either weekly or every other week.

The efficacy and safety findings in the Phase I study were validated in the Phase II trial presented at ASH. The Phase II trial included 143 patients treated on a weekly dose and 145 patients treated at a higher biweekly dose.

The overall response rate in these two groups was about 73%, Chari said. The response rate was maintained throughout various subgroups examined, with the exception of patients with a rare form of multiple myeloma that also extends to organs and soft tissues. More than 30% of patients in both groups had a complete response (no detection of myeloma-specific markers) or better, and nearly 60% had a “very good partial response” or better (indicating the cancer was substantially reduced but not necessarily down to zero).

The median time to a measurable response was approximately 1.2 months in both dosing groups and the median duration of response to date is 9.3 months with weekly dosing. Researchers are continuing to collect data on the duration of response in the group receiving 0.8 mg/kg every other week and for patients in both dosing groups who had a complete response or better.

Side effects were relatively frequent, but typically mild. About three-quarters of patients experienced cytokine release syndrome—a constellation of symptoms including fever that is common with immunotherapies. About 60% experienced skin-related side effects such as rash, about half reported taste changes, and about half reported nail disorders. The researchers said very few patients (5–6%) stopped talquetamab treatment because of side effects.

The response rate observed in the study, which Chari explained is higher than that for most currently accessible therapies, suggests talquetamab could offer a viable option for patients whose myeloma has stopped responding to most available therapies, offering a chance to extend life and benefit from other new and future therapies as they are developed.

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