On July 31, 2023 the CDE official reported that Janssen’s universal T-cell redirecting BCMAxCD3 bispecific antibody teclistamab (Tecvayli) has been included in a breakthrough therapy for the treatment of relapsed or refractory multiple myeloma ( r/r MM) adult patients whose prior therapy included a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody (Press release, Johnson & Johnson, JUL 31, 2023, View Source [SID1234633516]).
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Previously, in June 2021, the FDA also granted Breakthrough Drug Designation (BTD) to teclistamab for the treatment of r/r MM. On August 25, 2022, the European Union approved the conditional marketing of teclistamab, the first approval of teclistamab worldwide.
teclistamab is a bispecific antibody that targets B cell maturation antigen (BCMA) and T cell CD3 receptor. The expression level of BCMA was significantly increased on multiple myeloma cells, and CD3 was involved in activating T cells. teclistamab redirects CD3+ T cells to BCMA+ myeloma cells, resulting in their lysis and killing by CTL. Preclinical findings show that teclistamab kills myeloma cells from overly pretreated patients.
The EU approval is based on positive results from a multi-cohort, open-label Phase 1/2 clinical trial, MajesTEC-1. Results of the trial showed an overall response rate (ORR) of 63% in 165 patients with rrMM who received weekly subcutaneous injections of teclistamab after a median follow-up of 14.1 months. It is worth mentioning that 59% of patients achieved a very good partial response (VGPR) or better response, and 39% of the patients achieved a complete response (CR) or higher response.
MM is a malignant disease characterized by abnormal proliferation of clonal plasma cells. It is the second most common malignant tumor in the blood system in many countries. At present, drug therapy is still the main treatment for relapsed or refractory multiple myeloma. According to the "CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies 2021", the use of immunomodulators, proteasome inhibitors and anti-CD38 antibodies is recommended for class I. The main drug classes are treated with 4-drug, 3-drug or 2-drug combination regimens, as shown in the figure below. However, the clinical prognosis of this treatment program is poor, and the remission rate is only 20%-30%.
Currently, on the CDE Clinical Trials Registry platform, teclistamab is conducting a trial comparing teclistamab in combination with daratumumab SC (Tec-Dara) versus daratumumab in subjects with relapsed or refractory multiple myeloma. An international multicenter phase III randomized study of anti-SC, pomalidomide and dexamethasone (DPd) or daratumumab SC, bortezomib and dexamethasone (DVd). To compare the efficacy of teclistamab in combination with daratumumab SC (Tec-Dara; arm A) with investigator-selected DPd or DVd (arm B), as assessed by progression-free survival (PFS). The international target enrollment number is 560, and the domestic target enrollment number is 56.