Tecvayli (teclistamab-cqyv)

Based on the results of this systematic review, BCMA-directed therapies such as CAR-T cell therapy and bispecific antibodies demonstrate promising efficacy among patients with anti-CD38 refractory disease. However, additional evidence from randomized clinical trials is necessary to establish best practice guidelines.

P=N/A, N=400, Recruiting, St. Olavs Hospital

P1, N=74, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Mar 2026 --> May 2027

P1, N=290, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2025 --> Apr 2027

P1/2, N=40, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Mar 2025 --> Apr 2026

P=N/A, N=600, Recruiting, Janssen-Cilag Ltd. | Trial primary completion date: Jan 2025 --> Jun 2025

P=N/A, N=600, Recruiting, Janssen-Cilag Ltd. | Trial completion date: Jan 2025 --> Jun 2025

P2, N=10, Not yet recruiting, Hospital Universitario Dr. Jose E. Gonzalez

P=N/A, N=600, Recruiting, Janssen-Cilag Ltd. | N=280 --> 600

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

P1, P2 | "Incidence of CRS upon restarting teclistamab after dosing intervals of >28 days was low. Two of 61 patients experienced CRS (grade 1–2) with restarting after >28–62-day dosing intervals with repeat SUD. Among 61 patients with prolonged dosing intervals, 59 did not experience CRS on restart."

P1 | "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."

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.

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