Tecvayli (teclistamab-cqyv)

Median number of prior lines was 4 (range 1-13), 19.4% had received CAR-T previously, and 12.9% had been previously exposed to another TCE.Twenty-three pts (74.2%) were enrolled in clinical trials (7 with teclistamab, Tec, 6 with talquetamab, Tal, and 10 with investigational agents). Twelve of these pts received TCE in combination with daratumumab and/or pomalidomide...MRD- seems to translate into long PFS, regardless of HR disease. Prospective studies on fixed duration treatment with TCE based on baseline risk and treatment response are needed.

P2, N=194, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2025 --> Jun 2026

P1/2, N=228, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P=N/A, N=100, Recruiting, Universitaire Ziekenhuizen KU Leuven | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Dec 2024

P2, N=75, Recruiting, SCRI Development Innovations, LLC | Trial completion date: Feb 2025 --> Aug 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

P1, N=20, Recruiting, University of Washington | Not yet recruiting --> Recruiting

Teclistamab (Tec), a bispecific antibody (BsAb) targeting BCMA, shows promise in refractory MM and, when combined with daratumumab (Tec-Dara), may help eliminate residual disease...Prior therapy exclusions apply, except for limited doses of dexamethasone, bortezomib, cyclophosphamide, lenalidomide, or daratumumab...The study seeks to determine if AHCT can be deferred in patients achieving MRD negativity after Dara-VRd without compromising the chance of reaching and sustaining MRD negativity, and whether post-AHCT Tec-Dara can enhance sustained MRD negativity rates compared to post-AHCT Dara-R in MRD-positive patients. The study is currently open for enrollment at multiple sites in the US.

P=N/A, N=20, Recruiting, Peking University People's Hospital

These retrospective clinical analyses show that teclistamab treatment can be restarted with minimal risk of CRS after prolonged treatment interruption when repeat SUD is implemented for interruptions of >62 days. These analyses were successfully informed using popPK modeling to recommend the appropriate intervals to repeat SUD when restarting teclistamab treatment, consistent with the European Medicines Agency–approved product label : if maintenance doses are delayed 8–62 days, continue teclistamab at the last maintenance dose and schedule; if delayed 63–111 days, restart teclistamab at SUD 2; if delayed >111 days, restart teclistamab at SUD 1.

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. Conclusions : 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...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.

Conclusions : 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

"This abstract is embargoed until Friday, June 14, 2024 (09:00 CEST). Presentation during EHA2024: All (e)Poster presentations will be made available as of Friday, June 14, 2024 (09:00 CEST) and will be accessible for on-demand viewing until Thursday, August 15, 2024 on the Congress platform."

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