Updated efficacy and safety results from the Teclistamab cohort of the phase 1b TriMM-2 study were presented at the 2022 European Hematology Association ( EHA ) Annual Congress

Teclistamab, a T-cell redirecting bispecific antibody targeting B-cell maturation antigen ( BCMA ) is being studied in combination with Daratumumab and Hyaluronidase ( Daratumumab and Hyaluronidase-fihj; Darzalex Faspro ) in patients with relapsed or refractory multiple myeloma ( RRMM ) who have received three or more prior lines of therapy.
Patients in the study, including a high proportion with prior anti-CD38 exposure, have achieved encouraging overall response rates ( ORR ) with this combination treatment.

At a median follow-up of 8.6 months ( range, 0.3-19.6 ), 76.5% ( 39/51 ) of response-evaluable patients enrolled in the study achieved a response, including 36 patients ( 70.6% ) who achieved a very good partial response ( VGPR ) or better.
In patients with prior anti-CD38 exposure, an ORR of 73.7% was achieved.
The median time to first confirmed response was one month, and responses remained durable and deepened over time.
At the analysis cutoff, 66.7% of patients who achieved a response ( 26/39 ) were alive and continuing on therapy.

The open-label, multicenter, multicohort phase 1b TriMM-2 study is investigating the safety and efficacy of Teclistamab in combination with Darzalex Faspro for patients with relapsed or refractory multiple myeloma.
Enrolled patients received a median of five prior lines of therapy, 58.5% were triple-class refractory, 30.8% were penta-drug refractory, and 63.1% were refractory to anti-CD38 treatment. Eighty percent of patients were refractory to their last line of therapy.

As of April 6, 2022, 65 patients received Daratumumab 800mg at the approved schedule plus Teclistamab 1.5mg/kg weekly ( QW ) or 3mg/kg every other week ( Q2W ) subcutaneously.
Pre-medications, including steroids, were limited to the two step-up doses and the first full dose of Teclistamab.

Treatment with the combination regimen were tolerable and no unexpected or overlapping toxicities were observed.
The most common adverse events were cytokine release syndrome ( CRS ) (67.7%, all grade 1 or 2 ); neutropenia ( 49.2%, 41.5% grade 3 or 4 ); and anemia ( 41.5%, 27.7% grade 3 or 4 ).
One patient ( 2% ) had grade 1 immune effector cell–associated neurotoxicity syndrome ( ICANS ) which fully resolved.
Infections were experienced by 67.7% of patients ( 27.7% grade 3 or 4 ).
Four patients died from adverse events, all unrelated to Teclistamab or Daratumumab treatment.

Pharmacodynamic analyses have demonstrated that the combination upregulates CD38+/CD8+ T-cells and proinflammatory cytokines, suggesting the potential for synergistic activity.
Additional studies are needed to fully understand the potential clinical benefit of this biological activity.

Teclistamab is a fully humanized, T-cell redirecting, IgG4 bispecific antibody targeting both BCMA ( B-cell maturation antigen ) and CD3, the T-cell receptor.
BCMA is expressed at high levels on multiple myeloma cells.
Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells. ( Xagena_2022 )

Source: Janssen Pharmaceutical, 2022

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