The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion recommending the conditional marketing authorization of teclistamab for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose cancer has worsened since receiving the last treatment.
The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use has adopted a positive opinion recommending the conditional marketing authorization of teclistamab (Tecvayli) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose cancer has worsened since receiving the last treatment.1
The recommendation is based on findings from the phase 1/2 MajesTEC-1 trial (NCT04557098, NCT03145181), which showed that at a median follow-up of 14.1 months, teclistamab elicited an overall response rate (ORR) of 63% (95% CI, 55.2%-70.4%) in patients with relapsed or refractory myeloma after at least 3 prior lines of therapy (n = 165).2 Additionally, teclistamab produced a complete response (CR) or better rate of 39.4%, and 58.8% of patients had a very good partial response (VGPR) or better.
Teclistamab is a BCMA- and CD3-targeted monoclonal antibody designed to bind to CD3 on T cells and BCMA on plasma cells to mediate T-cell activation and subsequent lysis of BCMA-expressing multiple myeloma cells.
The first-in-human, open-label, multicohort, multicenter, dose-escalation MajesTEC-1 trial investigated the agent in patients with relapsed or refractory multiple myeloma who previously received 3 or more lines of therapy and who were triple-class exposed.
Patients were required to have measurable disease and to have previously received a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Patients could not have previously received a BCMA-directed therapy. In the phase 1 portion of the trial, patients were relapsed, refractory, or intolerant to established therapies, and in the phase 2 portion, they previously received 3 or more lines of therapy.
Enrolled patients received step-up doses of subcutaneous teclistamab at 60 µg/kg and 300 µg/kg during the first week of treatment. In cycle 1 and beyond, teclistamab was administered at 1500 µg/kg per week until disease progression.
ORR served as the trial’s primary end point. Secondary end points included duration of response (DOR), VGPR or better rate, CR or better rate, stringent CR rate, time to response, minimal residual disease status, progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics, immunogenicity, and patient-reported outcomes.
The median age of enrolled patients was 64.0 years (range, 33-84), and 14.5% of patients were at least 75 years old. The majority of patients were male (58.2%), White (81.2%), had an ECOG performance status of at least 1 (66.7%), had International Staging System class I disease (52.5%), underwent prior stem cell transplantation (81.8%), and were penta-drug exposed (70.3%).
The median number of prior lines of therapy was 5 (range, 2-14), and refractory status included an immunomodulatory agent (92.1%), proteasome inhibitor (86.1%), anti-CD38 monoclonal antibody (89.7%), triple-class (77.6%), and penta-drug (30.3%). Additionally, 89.7% of patients were refractory to their last line of treatment.
Additional data showed that the median DOR was 18.4 months (95% CI, 14.9–not estimable [NE]). The median time to first response was 1.2 months (range, 0.2-5.5), and the median time to best response was 3.8 months (range, 1.1-16.8). Furthermore, the MRD negativity rate was 26.7% (95% CI, 20.1%-34.1%), and among the 65 patients to achieve a CR or better, the MRD negativity rate was 46%.
The median PFS was 11.3 months (95% CI, 8.8-17.1), and the median OS was 18.3 months (95% CI, 15.1-NE).
Regarding safety, all patients experienced at least 1 adverse effect (AE) of any grade, and 94.5% of patients had a grade 3 or 4 AE. The most common any-grade AEs included cytokine release syndrome (CRS; 72.1%), neutropenia (70.9%), anemia (52.1%), thrombocytopenia (40%), lymphopenia (34.5%), diarrhea (28.5%), fatigue (27.9%), and nausea (27.3%). Although CRS was the most common any-grade AE, only 1 patient experienced a grade 3 or 4 CRS event.
In December 2021, a biologics license application seeking the approval of teclistamab in patients with relapsed or refractory multiple myeloma was submitted to the FDA, which was also based on findings from MajesTEC-1.3