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Phase 1b results for Daratumumab in combination with Teclistamab, a BCMA x CD3 bispecific antibody, for the treatment of relapsed / refractory multiple myeloma


Teclistamab is a BCMA × CD3 T-cell redirecting bispecific antibody under investigation in patients with relapsed / refractory multiple myeloma ( RRMM ).
Daratumumab ( Darzalex Faspro) is a CD38 monoclonal antibody ( mAb ) with direct on-tumor and immunomodulatory actions.
Initial clinical data from the phase 1b multicohort TRIMM-2 study have supported the combination of Teclistamab + Daratumumab for the treatment of relapsed / refractory multiple myeloma, with tolerable safety, no overlapping toxicities, and promising efficacy.

Researchers have updated results with additional patients and longer follow-up.

Eligible patients with multiple myeloma aged 18 years or more had received 3 or more prior lines of therapy ( LOT; including a proteosome inhibitor [ PI ] and immunomodulatory drug [ IMiD ] ) or were double-refractory to a PI and IMiD.
Patients treated with anti-CD38 therapy 90 days or less prior were excluded.
Patients received Daratumumab subcutaneous ( SC ) 1800 mg per approved schedule and Teclistamab SC 1.5–3 mg/kg once-weekly ( QW ) or every 2 weeks ( Q2W ).

Primary objectives were to identify the recommended phase 2 dose of Teclistamab for combination therapy and evaluate safety of the combination.
Responses were assessed by IMWG criteria.
Adverse events were graded per CTCAE v5.0; cytokine release syndrome ( CRS ) and immune effector cell-associated neurotoxicity syndrome ( ICANS ) were graded per ASTCT guidelines.

At data cutoff ( Jan 13, 2022; safety population: n=46 ), median follow-up was 7.2 months ( range 0.1–16.6; median age 67 years [ range 50–79 ]; 52% female ).
Patients received a median of 6 prior LOT ( range 2–17; 74% triple-class exposed; 63% penta-drug exposed; 15% anti-BCMA exposed ).

91% of patients had 1 or more adverse events ( grade 3/4 78% ), most commonly CRS ( 61%; all grade 1/2; median time to onset 2 days; median duration 2 days ), neutropenia ( 54%; grade 3/4 50% ), anemia ( 46%; grade 3/4 28% ), thrombocytopenia ( 33%; grade 3/4 28% ), and diarrhea ( 33%; grade 3/4 2% ).
Infections occurred in 29 patients ( 63%; grade 3/4 28% ).
One patients had grade 1 ICANS that fully resolved.
Among 37 response-evaluable patients, ORR was 78% ( 29/37 ); 27 patients ( 73% ) had very good partial response ( VGPR ) or better.

Median time to first response across dosing cohorts was 1.0 month ( range 0.9–2.8 ); median duration of response was not reached.
Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed with Teclistamab + Daratumumab, supporting potential synergy of the combination in patients with prior anti-CD38 exposure.

In conclusion, Teclistamab + Daratumumab has provided a novel immunotherapy approach for the treatment of RRMM that may yield improved clinical efficacy in heavily pretreated patients. ( Xagena )

Rodríguez-Otero P et al, J Clin Oncol 2022 ( 40 suppl 16; abstr 8032 )

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