‘Exciting’ responsiveness to talquetamab for r/r MM

Three cohorts, two doses

The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.

There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.

The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.

The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
 

Phase 2 results

The overall response rate (ORR)  among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).

The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.

The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).

The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
 

Safety profile

Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.

Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.

Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.

Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases  with dose reductions.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
 

What’s next?

At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)

Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.

Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.

A version of this article first appeared on Medscape.com.