The European Commission ( EC ) has granted the approval of a Type II variation application for Tecvayli ( Teclistamab), providing the option for a reduced dosing frequency of 1.5mg/kg every two weeks in patients who have achieved a complete response ( CR ) or better for a minimum of six months.
Teclistamab was the first bispecific antibody targeting B-cell maturation antigen ( BCMA ) on multiple myeloma cells, and CD3 on T-cells, to receive approval in Europe for the treatment of adult patients with relapsed and refractory multiple myeloma ( RRMM ) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 antibody, and have demonstrated disease progression on the last therapy.
The EC approval was supported by positive results from the phase 1/2 MajesTEC-1 study, evaluating the safety and efficacy of Teclistamab in patients with relapsed and refractory multiple myeloma.
Patients in the study had received a median of five prior lines of therapy ( range, 2-14 ) and, following an initial step-up phase, were initially treated with the recommended phase 2 dose ( RP2D ) of 1.5 mg/kg Teclistamab weekly ( QW ) administered subcutaneously.
Patients who had achieved a confirmed partial response ( PR ) or better after four or more cycles of treatment ( Phase 1 ), or a confirmed CR or better for six months or longer ( Phase 2 ) were eligible to reduce dosing frequency to 1.5 mg/kg subcutaneously every two weeks ( Q2W ) until disease progression or unacceptable toxicity.
Of 104/165 responders who had received Teclistamab at the RP2D, 63 patients switched to Q2W dosing.
Results from the analysis have shown that at the time of switch, 85.7% of patients has achieved a complete response or better, 12.7% has achieved a very good partial response ( VGPR ) and 1.6& has achieved a partial response.
The median time to switch from first QW to first Q2W dose was 11.3 months ( range, 3-30 ).
At a median follow-up of 12.6 months ( range, 1-25 ) since switching, the median duration of response was not yet reached and 68.7% ( 95% Confidence Interval [ CI ], 53.6-79.7 ) of patients who switched remained in response for two or more years from the time of first response.
The new onset of grade 3 or higher infections after 12-18 months of follow up was lower in responders who switched to Q2W dosing on or before 12 months compared to those who remained on QW dosing at 12 months ( 15.6% vs 33.3% ).
As of data cutoff, 41 patients ( 65% ) remained on treatment.
MajesTEC-1 is a phase 1/2 single-arm, open-label, multicohort, multicentre dose-escalation study to evaluate the safety and efficacy of Teclistamab in adults with relapsed and refractory multiple myeloma who received three or more prior lines of therapy ( n=165 ).
Phase 1 of the study was conducted in two parts: dose escalation ( Part 1 ) and dose expansion ( Part 2 ). It evaluated safety, tolerability, pharmacokinetics, and preliminary efficacy of Teclistamab in adult participants with relapsed and refractory multiple myeloma.
Phase 2 of the study has evaluated the efficacy of Teclistamab at the RP2D, established at subcutaneous 1.5 mg/kg weekly, as measured by overall response rate.
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. In multiple myeloma, these malignant plasma cells change and grow out of control.
In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,400 patients died.
While some patients with multiple myeloma initially have no symptoms, others can have common symptoms of the disease which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure. ( Xagena )
Source: Janssen Pharmaceutical, 2023