Tecvayli (teclistamab-cqyv)

Currently, two BCMA-targeting BsAbs (teclistamab and elranatamab) and one GPRC5D-targeting BsAb (talquetamab) have regulatory approval for the treatment of patients (pts) with RRMM. CMMC counts through serial peripheral blood sampling can be used to assess disease burden and early kinetics of response to BsAb therapy. Further follow-up and additional cohorts are planned to confirm performance of this assay as a biomarker in predicting response and long-term outcomes in patients receiving BsAb and other therapies, as well as interrogating mechanisms of resistance through targeted sequencing and analysis of tumor-associated antigens of enumerated cells.

B-cell maturation antigen (BCMA)-targeting bispecific T-cell engagers (BiTEs), Teclistimab and Elranatamab have shown rapid and durable responses in RRMM with a lower incidence and severity of cytokine release syndrome (CRS) compared to chimeric antigen receptor T-cell therapies...CRS occurred within 24 hours of the first priming dose, lasted two days, and resolved with IV fluids, tocilizumab, and dexamethasone without recurrence... In this case series of heavily pre-treated Daratumumab relapsed/ refractory AL amyloidosis patients with advanced cardiac involvement, Elranatamab elicited rapid and deep hematological responses with all patients achieving a hematological complete response with deep suppression of iFLC within two weeks of treatment initiation, including MRD negative disease and cardiac responses in all tested patients after 3-5 cycles. Elranatamab was well-tolerated with no added toxicity and acceptable safety profile. These data support Elranatamab’s use in relapsed/refractory AL amyloidosis and prospective studies using BCMA-targeting BiTEs in this high-risk, high-need population.

Tal-DP exhibits a deep, long-term impact on efficacy through complementary mechanisms of action and may be especially beneficial in pts with prior BsAb exposure, who typically have unfavorable BL immune profiles. Ongoing analyses of tec-DP from MajesTEC-2 (NCT04722146) will be presented.

P2, N=300, Recruiting, Multiple Myeloma Research Consortium | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Nov 2024

P1, N=290, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Sep 2024 --> Aug 2025

P3, N=650, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Oct 2025 --> Feb 2026

P2, N=130, Recruiting, University of Heidelberg Medical Center | N=70 --> 130 | Trial completion date: Oct 2027 --> Aug 2028 | Trial primary completion date: Oct 2026 --> Feb 2027

P2, N=30, Not yet recruiting, European Myeloma Network B.V.

"With the longest follow-up of any BsAb in MM, tec continues to demonstrate deep and durable responses, including in pts switching to less frequent dosing. The tec safety profile remains consistent with BCMA-targeted BsAb, with a notable decrease in new-onset severe infections with time."

P1, N=74, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Sep 2024 --> Feb 2025

P1, N=302, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P1, N=20, Not yet recruiting, University of Washington

P1, P2 | "With the longest follow-up of any BsAb in MM, teclistamab continues to demonstrate deep and durable responses, including in patients who switch to less frequent dosing. The teclistamab safety profile remains consistent with that of BCMA-targeted bispecific therapies, with a notable decrease in new onset of severe infections with time."

P2, N=40, Recruiting, Janssen Research & Development, LLC

P4, N=15, Not yet recruiting, University Health Network, Toronto | Initiation date: Apr 2024 --> Oct 2024

P2, N=75, Recruiting, SCRI Development Innovations, LLC | N=50 --> 75

P1, N=74, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=152 --> 74

P2, N=74, Recruiting, University Hospital, Lille | Not yet recruiting --> Recruiting

P1, N=152, Recruiting, Janssen Research & Development, LLC | Trial completion date: Nov 2025 --> Mar 2026

P2, N=50, Recruiting, North Estonia Medical Centre

P=N/A, N=100, Not yet recruiting, Universitaire Ziekenhuizen KU Leuven

P=N/A, N=280, Recruiting, Janssen-Cilag Ltd. | N=200 --> 280 | Trial completion date: Jan 2026 --> Nov 2024

P1, N=100, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

P=N/A, N=200, Recruiting, Janssen-Cilag Ltd. | Trial primary completion date: Jul 2024 --> Nov 2024

P1, N=100, Not yet recruiting, Janssen Research & Development, LLC

Teclistamab continues to demonstrate deep and durable responses, including in pts who switch to less frequent dosing. The safety profile of teclistamab remains consistent with that of BCMA-targeted bispecific therapies, with a notable decrease in new onset of severe infections with time.

Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.

Primary resistance is characterized by a low T-cell/MM cell-ratio and Treg-driven immunosuppression, while reduced T-cell fitness due to continuous BsAb-mediated T-cell activation may contribute to development of acquired resistance.

P=N/A, N=180, Recruiting, Janssen-Cilag Ltd. | Trial completion date: Jul 2024 --> Jan 2026

P3, N=795, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jun 2027 --> Apr 2026

These findings illustrate the importance of the contribution of the immune landscape to T-cell redirection therapy response. This trial was registered at www.ClinicalTrials.gov, NCT03145181/NCT04557098.

P2, N=20, Not yet recruiting, Case Comprehensive Cancer Center

P2, N=103, Not yet recruiting, Nantes University Hospital

P3, N=1590, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: May 2029 --> Apr 2031

P1, N=289, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2024 --> Aug 2025

P3, N=587, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Oct 2026 --> Dec 2028

P1, N=282, Recruiting, Janssen Research & Development, LLC | Trial completion date: Mar 2026 --> Jul 2026

P=N/A, N=180, Recruiting, Janssen-Cilag Ltd.

P1, N=140, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jun 2024 --> Oct 2024

P4, N=15, Not yet recruiting, University Health Network, Toronto

P3, N=795, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

P3, N=795, Not yet recruiting, Janssen Research & Development, LLC