Ajai Chari, MD, Professor of Medicine and Director of Clinical Research, Multiple Myeloma Program, Mount Sinai School of Medicine, discusses results from the phase 1/2 MonumenTAL-1 clinical trial. These results were recently presented at this year’s American Society of Hematology Meeting & Exposition (ASH 2022).
Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. Symptoms of multiple myeloma may include: bone pain (particularly in the chest and spine), frequent infections, weakness or numbness in the legs, fatigue, confusion, excessive thirst, and constipation. While the cancer is treatable, relapses are common and some patients are refractory to first line treatment.
As Dr. Chari explains, MonumenTAL-1 is a phase 1/2 trial of talquetamab in patients with relapsed/refractory multiple myeloma. Talquetamab is a bispecific antibody that targets both GPRC5D and CD3 on T cells. Data from phase 1 of MonumenTAL-1 supported the selection of two recommended phase 2 doses for talquetamab: 0.405 mg/kg subcutaneously QW (modified to 0.4 mg/kg in phase 2 for convenience) and 0.8 mg/kg subcutaneously Q2W.
The primary endpoint of phase 2 was overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria based on independent committee review. Key secondary endpoints were duration of response (DOR), rate of very good partial response or better (≥VGPR), rate of complete response or better (≥CR), time to response, progression-free survival (PFS), and incidence of AEs.
As of May 16, 2022, 288 pts with no prior exposure to T-cell redirecting therapies had received talquetamab at the recommended doses in phase 1 or 2. Baseline characteristics were similar among both treatment dose groups.
In the 143 patients treated at 0.4 mg/kg QW, results were published and available here. In that group, ORR was 73% (≥VGPR: 58%; ≥CR: 29%). Responses were durable and deepened over time. Median time to response was 1.2 months. Median time to CR was 2.1 months. Median DOR was 9.3 months. Median PFS was 7.5 months. ORRs in patients who were triple-class refractory (72% [76/106]) and penta-drug refractory (71% [30/42]) were comparable to the overall population.
Talquetamab exposure was comparable at the two recommended doses. No clinically significant effect of anti-talquetamab antibodies on PK, efficacy, or AEs was observed. Additionally, pharmacodynamic changes were comparable at both recommended doses and were consistent with talquetamab activity, including T-cell activation, redistribution, and induction of cytokines.
The most common adverse events at 0.4 mg/kg QW / 0.8 mg/kg Q2W were cytokine release syndrome (79%/72%), dysgeusia (48%/46%), and anemia (45%/39%). Skin-related adverse events occurred in 56%/68% of patients and nail disorders occurred in 52%/43% of patients. Cytopenias, including neutropenia in 34%/28% and thrombocytopenia in 27%/27% of patients, were generally limited to the first few cycles. Infections occurred in 57%/50% of patients. 4.9%/6.2% of patients discontinued, 8.4%/13.8% had dose delays, and 14.7%/6.2% had dose reductions due to adverse events. There were two deaths due to COVID-19 (one patient at each recommended dose).
Overall, talquetamab demonstrated strong efficacy and a manageable safety profile in patients with heavily pretreated relapsed/refractory multiple myeloma.
To learn more about multiple myeloma and other rare cancers, visit checkrare.com/diseases/cancers/
