In the first combination study of talquetamab and teclistamab in patients with relapsed or refractory multiple myeloma (R/R MM), the drug combination had a manageable safety profile consistent with each of the monotherapies. Moreover, the drug combination was effective in patients with advanced R/R MM, including those with extramedullary disease (EMD), which is typically a difficult-to-treat population.
The initial results from the phase Ib RedirecTT-1 trial were presented by Yael C. Cohen, MD, of Tel Aviv University in Israel, on June 3 at the American Society of Clinical Oncology (ASCO) Annual Meeting.
Teclistamab is the first B-cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of triple-class exposed R/R MM. Talquetamab, a bispecific antibody targeting the novel myeloma antigen G protein-coupled receptor, class C, group 5, member D (GPRC5D), has shown efficacy in patients with R/R MM.
“It was hypothesized that combining an approach targeting two distinct antigens found in MM cells may overcome some resistance mechanisms to monotherapy by reducing the risk of the loss of activity to a single target antigen and enhancing the antigen/antibody interaction,” Dr. Cohen said.
The study enrolled patients with MM who were relapsed or refractory or intolerant to the last line of therapy; were exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy; and had measurable disease. The primary objectives were to evaluate safety and to identify a recommended phase II regimen (RP2R) for the drug combination.
The RP2R comprised teclistamab 3.0mg/kg and talquetamab 0.8 mg/kg, “both administered every two weeks,” Dr. Cohen explained. “We also looked at preliminary anticancer activity as the secondary endpoint.”
As of December 12, 2022, a total of 63 patients with a median age of 67 years (range = 39-81) received talquetamab and teclistamab. The patients had received a median of five prior lines of therapy, 33% had high-risk cytogenetics, 78% were triple-class refractory, 63% were penta-drug exposed, and 43% had bone independent EMD.
With a median follow-up of 14.4 months, the most common treatment-emergent adverse events were cytokine release syndrome (81%), neutropenia (76%), and anemia (60%). Dose-limiting toxicities were reported at dose level 1, which included grade 3 herpetic stomatitis, and dose level 3, which included grade 3 aspartate aminotransferase/alanine aminotransferase elevation. One immune effector cell-associated neurotoxicity syndrome (ICANS) event was reported at dose level 3. No dose-limiting toxicities were reported at the RP2R.
Across all dose levels, the overall response rate (ORR) was 84% among the 62 evaluable patients and 73% among the 26 evaluable patients with EMD; the rate of complete response (CR) or better was 34% and 31%, respectively. At the RP2R, the ORR was 92% among all 13 evaluable patients and 83% among the six patients with EMD; the rate of CR or better was 34% and 31%, respectively. The median duration of response has not been reached.
“These results support the initiation of larger studies,” Dr. Cohen said. “The RedirecTT-1 expansion cohort with EMD is opening shortly based on these promising results.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Cohen YC, Morillo D, Gatt ME, et al. First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Abstract 8002. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 3, 2023; Chicago, Illinois.
