NEW ORLEANS — A novel, off-the-shelf antibody, talquetamab, has shown precocious effect rates among patients with heavy pretreated multiple myeloma successful some signifier 1 and present signifier 2 studies, which person been submitted for approval.
"Talquetamab is simply a caller cause directed against a caller antigen people successful myeloma," explained pb researcher Ajai Chari, MD, from the Mount Sinai School of Medicine successful New York City.
The merchandise has demonstrated "a effect complaint of 73% to 74% with some play and each 2-week schedules successful a heavy treated diligent population. Even successful those patients with anterior T-cell redirection we spot a 63% effect rate," Chari reported the data present astatine the American Society of Hematology (ASH) yearly meeting.
It is encouraging to spot precocious effect rates among patients with illness that is refractory to aggregate anterior lines of therapy, and the results suggest that talquetamab whitethorn bargain clip for patients with fewer different options, commented Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center successful Seattle, Washington, and a erstwhile ASH president.
"It looks similar determination are responses adjacent successful radical who are heavy pretreated, and person had different agents akin to it, " she said. "We perceive astir 'penta-refractory' [disease] and everything, and I deliberation we're going to commencement proceeding astir 'octo-refractory' and 'deci-refractory' and those things. It's truly breathtaking [to spot these responses]," she said. Lee moderated a media briefing anterior wherever Chari discussed the information anterior to his presentation.
Talquetamab is simply a bispecific antibody directed against a caller people with the prosaic sanction of "G protein–coupled receptor, household C, radical 5, subordinate D" oregon simply GPRC5D. The antigen is simply a alleged "orphan" receptor with an unidentified ligand. The receptor is expressed successful malignant plasma cells, making it a peculiarly charismatic people for the attraction of patients with aggregate myeloma.
"It's important to prime the close people for these [patients] and GPRC5D is simply a bully campaigner for that due to the fact that it's highly expressed connected myeloma cells but spares mean tissues, successful peculiar the hematopoietic stem cells for the precursors to their blood," Chari said.
The caller cause could beryllium disposable adjacent year. The manufacturer, Janssen, announced connected past week that it had submitted an support application with the Food and Drug Administration for talquetamab usage successful the treatment of patients with relapsed oregon refractory aggregate myeloma.
The objective results truthful acold "indicate the imaginable of this attraction for heavy pretreated patients who person exhausted presently approved therapies," Chari said successful a statement.
MonumenTAL Study
Chari and colleagues precocious reported results of the phase I MonumenTAL-1 study successful The New England Journal of Medicine. Here astatine ASH 2022, they reported signifier 2 results from the aforesaid study, including immoderate patients carried implicit from signifier 1, but besides a subgroup of patients with anterior vulnerability to either chimeric antigen receptor T-cell (CAR-T) therapy oregon different bispecific T cell-engaging antibodies.
In the signifier I dose-escalation survey published successful NEJM, the effect rates among patients who had a median of six anterior lines of therapy ranged from 64%-70%. The cause was delivered successful this signifier astatine a assortment of dose levels and schedules, and some intravenously and subcutaneously.
Three Cohorts, Two Doses
The signifier 2 survey enrolled patients who had a minimum of 3 anterior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair show status.
There were 3 cohorts. The archetypal cohort included 21 patients from signifier 1 and 122 from signifier 2 who received talquetamab astatine a dose of 0.4 mg/kg subcutaneously erstwhile weekly. These patients were allowed to person received anterior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not person received a anterior T-cell redirection therapy.
The 2nd cohort included 36 patients successful signifier 1 and 109 successful signifier 2 who were treated with 0.8 mg/kg subcutaneously each 2 weeks. These patients had the aforesaid anterior therapy allowances and restrictions arsenic the archetypal cohort.
The 3rd cohort included 17 patients successful signifier 1 positive 34 successful signifier 2 who had received either CAR T-cell receptor therapy oregon a antithetic bispecific T-cell engager. These patients received either 0.4 mg/kg play subcutaneous talquetamab, oregon 0.8 mg/kg each 2 weeks.
Phase 2 Results
The wide effect complaint (ORR) among patients treated astatine 0.4 mg/kg play was 74.1%, including 23.8% stringent implicit responses (sCR), 9.8% implicit effect (CR), 25.9% precise bully partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated astatine the 0.8 mg/kg each 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The effect rates were accordant crossed subgroups, including baseline International Staging System (ISS) signifier III disease, baseline cytogenetic risk, fig of anterior therapies, grade of refractoriness to anterior therapy, and anterior vulnerability to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months successful the 0.4 and 0.8 mg/kg doses, respectively. The median duration of effect was not reached among patients who had achieved a CR oregon amended successful either dosing group.
Safety Profile
Most adverse events of people 3 oregon 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were mostly constricted to the archetypal 3 cycles, and little than a 3rd of each cytopenias were people 3 oregon greater.
Infection occurred successful 57.3% of patients treated astatine 0.4 mg/kg play and 50.3% treated astatine 0.8 mg/kg each 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were people 3 oregon 4.
Opportunistic infections were seen successful 3.5% of patients treated astatine 0.4 mg/kg and 2.8% of those treated astatine 0.8 mg/kg.
Taste alterations (dysgeusia) occurred successful astir fractional of patients successful each dosing group. Dysgeusia was managed with supportive care, including hydration, and successful immoderate cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed successful 10% to 11% of patients, but astir of these events were people 1 oregon 2.
What's Next?
At the briefing, Medscape Medical News asked Chari whether, fixed the evident efficacy and comparative information of this agent, it could beryllium moved up higher successful the therapeutic lines and combined with different agents specified arsenic proteasome inhibitors (bortezomib et al), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Chari replied that respective studies combining talquetamab with agents successful each of these classes and with different bispecific T-cell engagers are presently underway.
The survey was supported by Janssen. Chari disclosed consulting fees from the company. Lee has received objective proceedings probe backing from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served arsenic a advisor to Incyte.
American Society of Hematology (ASH) 2022 Annual Meeting: Abstract 157. Presented December 10, 2022.
Neil Osterweil, an award-winning aesculapian journalist, is simply a long-standing and predominant contributor to Medscape.
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