Talquetamab produced responses in more than 70% of patients with relapsed/refractory multiple myeloma (MM) who received the recommended phase 2 doses, according to research presented at the 2022 ASH Annual Meeting.1
Talquetamab is a bispecific antibody targeting GPRC5D on MM cells and CD3 on T cells. Researchers tested talquetamab in patients with relapsed/refractory MM in the phase 1/2 MonumenTAL-1 trial (ClinicalTrials.gov Identifiers: NCT03399799, NCT04634552).
In the phase 1 portion of the trial, researchers identified 2 recommended phase 2 doses of talquetamab given subcutaneously: 0.4 mg/kg weekly and 0.8 mg/kg every other week (Q2W).
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A total of 288 patients received talquetamab at the recommended phase 2 doses — 143 at 0.4 mg/kg weekly and 145 at 0.8 mg/kg Q2W.
Results in the Weekly Dosing Group
In the 0.4 mg/kg-weekly group, the median age at baseline was 67 (range, 46 to 86) years, and 89.5% of patients were White. The patients had received a median of 5 prior lines of therapy (range, 2 to 13), 74.1% had triple-class refractory disease, 29.4% had penta-refractory disease, and 93.7% had disease that was refractory to the last line of therapy.
The median follow-up for efficacy was 14.9 months. The overall response rate (ORR) was 74.1%, with 59.4% of patients achieving a very good partial response (VGPR) or better. This includes 9.8% of patients who achieved a complete response (CR) and 23.8% who achieved a stringent CR.
The ORR was 72.6% in patients who were triple-class refractory and 71.4% in patients who were penta-drug refractory.
The median duration of response was 9.3 months overall, but it was not reached for patients who achieved a CR or stringent CR. The median progression-free survival was 7.5 months.
The median follow-up for safety was 11.0 months. Cytokine release syndrome (CRS) occurred in 79.0% of patients. Three patients had grade 3 CRS (2.1%), and no cases of grade 4 CRS occurred.
Other common adverse events (AEs) were infections (57.3%), dysgeusia (48.3%), skin-related AEs (55.9%), nail disorders (51.7%), anemia (44.8%), neutropenia (34.3%), lymphopenia (28.0%), and thrombocytopenia (27.3%).
A total of 13 patients had immune effector cell-associated neurotoxicity syndrome (ICANS). Most cases were grade 1-2, 2 cases were grade 3, and there were no grade 4 cases.
One death occurred due to COVID-19 in this group.
Results in the Q2W Dosing Group
In the 0.8 mg/kg Q2W group, the median age at baseline was 67 years (range, 38 to 84), and 86.2% of patients were White. The patients had received a median of 5 prior lines of therapy (range, 2 to 17), 69.0% had triple-class refractory disease, 23.4% had penta-refractory disease, and 94.5% had disease that was refractory to the last line of therapy.
The median follow-up for efficacy was 8.6 months. The ORR was 73.1%, with 57.2% of patients achieving a VGPR or better, 12.4% achieving a CR, and 20.0% achieving a stringent CR.
The ORR was 71.0% in patients who were triple-class refractory and 70.6% in patients who were penta-drug refractory.
The median duration of response was 13.0 months overall, but it was not reached for patients who achieved a CR or stringent CR. The median progression-free survival was 11.9 months.
The median follow-up for safety was 5.1 months. CRS occurred in 72.4% of patients. One patient had grade 3 CRS, and there were no cases of grade 4 CRS.
Other common AEs included infections (50.3%), dysgeusia (46.2%), skin-related AEs (67.6%), nail disorders (43.4%), anemia (39.3%), neutropenia (28.3%), lymphopenia (26.2%), and thrombocytopenia (26.9%).
At total of 11 patients had ICANS. Most cases were grade 1-2, 2 cases were grade 3, and there were no grade 4 cases.
One death occurred due to COVID-19 in this group.
Results in Patients With Prior T-Cell Redirection Therapy
The researchers also looked at patients from both dosing groups who had received T-cell redirection therapy prior to study entry.
In this group, the ORR was 62.7% overall, 72.2% in patients with prior chimeric antigen receptor T-cell therapy, and 44.4% in patients with prior bispecific antibody treatment.
Overall, 52.9% of patients achieved a VGPR or better, 5.9% achieved a CR, and 17.6% achieved a stringent CR. At a median follow-up of 11.8 months, the median duration of response was 12.7 months.
The safety profile was comparable to that seen in patients without prior T-cell redirection therapy.
Results from this trial were also published in The New England Journal of Medicine.2
Disclosures: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
References
1. Chari A, Touzeau C, Schinke C, et al. 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. Presented at ASH 2022. December 10-13, 2022. Abstract 157.
2. Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell–redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. Published online December 10, 2022. doi:10.1056/NEJMoa2204591
