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Tecvayli based on Teclistamab, the first bispecific T-cell engager antibody for the treatment of patients with relapsed or refractory multiple myeloma. FDA has approved

The FDA ( U.S. Food and Drug Administration ) has approved Tecvayli ( Teclistamab-cqyv; Teclistamab ) for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

Teclistamab is a first-in-class, bispecific T-cell engager antibody that is administered as a subcutaneous treatment.
Teclistamab activates the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen ( BCMA ) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

The pivotal phase 2 MajesTEC-1 clinical trial has included patients who had received a median of five prior lines of therapy ( n=110 ).
An overall response rate ( ORR ) of 61.8% ( 95% Confidence Interval [ CI ]: 52.1%, 70.9% ) was achieved, notably with 28.2% of patients achieving a complete response ( CR ) or better ( CR or stringent complete response [ sCR ] ).
The median time to first response was 1.2 months ( range 0.2 to 5.5 months ).
With a median follow-up of 7.4 months, the estimated duration of response ( DoR ) rate was 90.6% ( 95% CI: 80.3%, 95.7% ) at six months and 66.5% ( 95% CI: 38.8%, 83.9% ) at nine months.
The study has included heavily pretreated patients, and 78% of patients received four or more prior lines of therapy.
All patients were triple-class exposed ( to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody ), and 76% were triple-class refractory ( to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody ).

The Safety Information for Teclistamab includes a Boxed Warning for cytokine release syndrome ( CRS ) and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome in addition to warnings and precautions for hepatotoxicity, infections, neutropenia, hypersensitivity and other administrative reactions and embryo-fetal toxicity.

The most common adverse reactions ( 20% or more ) in the safety population of MajesTEC-1 ( n=165 ) were pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea.
The most common Grade 3 to 4 laboratory abnormalities ( 20% or more ) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin and decreased platelets.

Tecvayli is available only through a restricted program called the Tecvayli Risk Evaluation and Mitigation Strategy.

Tecvayli is supplied as 30mg/3mL and 153mg/1.7mL single-dose vials.

MajesTEC-1 is a phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study to evaluate the safety and efficacy of Teclistamab in adults with relapsed or refractory multiple myeloma who received three or more prior lines of therapy.

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 or refractory multiple myeloma. Study criteria excluded patients who had stroke, seizure, allogenic stem cell transplantation within the past six months, ECOG performance score of 2 or higher, known active central nervous system ( CNS ) involvement or clinical signs of meningeal involvement of multiple myeloma, or active or documented history of autoimmune disease, with the exception of vitiligo, type 1 diabetes, and prior autoimmune thyroiditis.

Phase 2 of the study evaluated the efficacy of Teclistamab at the recommended phase 2 dose ( RP2D ), established at subcutaneous 1.5 mg/kg weekly, as measured by overall response rate. During week one, participants received step-up doses of Teclistamab subcutaneous ( 0.06 and 0.3 mg/kg ). Subsequently, participants received weekly treatment doses of Teclistamab subcutaneous 1.5 mg/kg until disease progression or unacceptable toxicity. Efficacy was established based on overall response rate as determined by the Independent Review Committee ( IRC ) assessment using International Myeloma Working Group ( IMWG ) 2016 criteria.

The primary endpoint was overall response rate or unacceptable toxicity. Secondary endpoints included duration of response, very good partial response, complete response, stringent complete response, time to response, minimal residual disease status, progression-free survival, overall survival, safety, pharmacokinetics, immunogenicity and patient-reported outcomes. ( Xagena )

Source: Janssen, 2022