Talquetamab shows ‘impressive’ efficacy for heavily pretreated advanced multiple myeloma
NEW ORLEANS — Nearly three-quarters of patients who received talquetamab for relapsed or refractory multiple myeloma had an objective response to therapy, results of the phase 1/phase 2 MonumenTAL-1 trial showed.
Data from the study — presented at ASH Annual Meeting and Exposition and published simultaneously in The New England Journal of Medicine — served as the basis for a biologics license application the agent’s manufacturer, Janssen, submitted to the FDA on Friday for treatment of patients with relapsed or refractory multiple myeloma.
“This is an exciting new treatment option for patients, and the safety was quite manageable,” Ajai Chari, MD, director of clinical research in the multiple myeloma program at The Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, told Healio.
“Patients definitely benefited from this therapy,” he added.
Background
Talquetamab is a T-cell-redirecting bispecific IgG4 antibody that binds to G protein-coupled receptor family C group 5 member (GPRC5D) and CD3.
GPRC5D is “an important target for treatment of multiple myeloma,” Chari said. This is because the antigen is highly expressed on malignant myeloid cells but less so by normal tissue.
The MonumenTAL-1 study sought to apply immunotherapy approaches using a novel target for the treatment of relapsed or refractory multiple myeloma that goes beyond currently available B-cell maturation antigen-targeted therapies, Chari said.
Methodology
The 288 patients treated in the trial received one of two recommended phase 2 doses: 0.4 mg/kg subcutaneously weekly (n = 143; median age 67 years; range, 46-86) or 0.8 mg/kg subcutaneously every other week (n = 145; median age 67 years; range 38-84).
Patients eligible for the phase 2 portion included those who experienced disease progression after three or more previous lines of therapy, including one or more proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.
Overall response rate using IMWG criteria as determined by an independent review committee served as the primary endpoint for the phase 2 portion of the study. Secondary endpoints included duration of response, complete response (CR) rate, PFS and safety.
Median follow-up was 11 months (range, 0.5-26.1) for those who received talquetamab dosed at 0.4 mg/kg subcutaneously weekly, whereas median follow-up was 5.1 months (range, 0.2-17.9) for those who received talquetamab at 0.8 mg/kg subcutaneously every other week. Sept. 12 served as the efficacy analysis data cutoff date for both dose groups.
Key findings
Investigators reported an ORR of 74.1%, with a complete response rate of 29% and very good partial response rate of 58% among those who received talquetamab dosed at 0.4 mg/kg subcutaneously weekly. Patients who received 0.8 mg/kg subcutaneously every other week demonstrated an ORR of 73.1%.
Researchers reported a median DOR of 9.3 months (range, 1-23; 95% CI, 6.6-12.7) and median PFS of 7.5 months (95% CI, 5.7-9.4) for the 0.4 mg/kg subcutaneously weekly group. They noted median DOR of 13 months (95% CI, 10 to not estimable) and median PFS of 11.9 months (95% CI, 8.4 to not estimable) among patients in the lower-dose group.
Cytokine release syndrome occurred in 79% of patients who received the 0.4 mg/kg dosing and 72% of those who received the 0.8 mg/kg dosing. Grade 4 or grade 5 CRS did not occur in either dose group.
Two patients died during the study due to COVID-19, including one patient in each phase 2 dose-level group.
Other common treatment-related adverse events included dysgeusia, anemia and cytopenias.
Infections occurred in more than half of patients regardless of the dose they received. Grade 3 or higher infections occurred in 16.8% of patients who received the 0.4 mg/kg dosing and 11.8% of those who received 0.8 mg/kg dosing.
Clinical implications
Talquetamab has the most mature data set of any T-cell-redirecting therapy tested to date in patients with multiple myeloma, according to Chari.
Whereas the response rates are “impressive” in his opinion, the safety profile of talquetamab should allow for it to be given in combination with other anticancer therapies, he said.
“We know that multiple myeloma is very hard to treat and that combination therapies are the way to move forward,” Chari told Healio.
Combination therapies with talquetamab are already being evaluated in ongoing studies and will be included as part of an upcoming confirmatory phase 3 trial, he added.
Collapse
Chari A, et al. Abstract 157. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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