Talvey (talquetamab-tgvs)

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.

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.

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

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=120, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P2, N=30, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2028 --> Feb 2027

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

P2, N=120, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

P2, N=30, Not yet recruiting, Stanford University | Initiation date: Jul 2024 --> Nov 2024

P2, N=30, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

These modeling results suggest that IL-6 release due to talquetamab-induced cytokine release syndrome has limited impact on potential drug-drug interactions, with the highest likelihood of impact occurring from initiation of talquetamab step-up dosing up to 7 (QW) or 9 (Q2W) days after first treatment dose in cycle 1 and during and after cytokine release syndrome. Multiple myeloma can be treated with immunotherapies such as the bispecific antibody, talquetamab, which binds the novel antigen G protein-coupled receptor family C group 5 member D on multiple myeloma cells and CD3 on T cells and induces T-cell-mediated lysis of multiple myeloma cells. Following talquetamab treatment, many patients experience cytokine release syndrome, an inflammatory immune response where levels of proinflammatory cytokines, including interleukin (IL)-6, are increased. Interleukin-6 can suppress the activity of important enzymes in the body (cytochrome [CYP] P450s) that are involved in drug clearance. This study used a physiologically based pharmacokinetic computer model to investigate the potential impact of increased IL-6 levels on CYP450 enzymes to determine subsequent impact on drugs that are metabolized by CYP450 enzymes. The results showed no predicted interaction between median levels of IL-6 observed in patients and CYP substrates (such as caffeine and omeprazole) with talquetamab. In a simulation that assessed higher (maximum) IL-6 levels observed in patients, the predicted impact of IL-6 was minimal to weak for most of the CYP substrates assessed. The effect on CYP450 enzymatic activity was highest from initiation of talquetamab step-up dosing up to 7-9 days after the first treatment dose of talquetamab. These results suggest that, in this treatment time period, elevated IL-6 levels due to talquetamab-induced cytokine release syndrome have limited impact on drugs that are CYP substrates that may be used in conjunction with talquetamab, but that the concentration and toxicity of these drugs should be monitored and the dose of CYP substrate adjusted as required.

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

P1/2, N=20, Not yet recruiting, City of Hope Medical Center

Oncology nurses have specialized knowledge of treatment administration monitoring based on their participation in the MonumenTAL-1 trial. This review provides information for nurses in both the academic and community settings on how to monitor, counsel, and support patients, which will in turn improve patients' quality of life and overall survival.

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

P1, N=167, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

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

P1, N=15, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Aug 2024 --> Aug 2025

P2, N=30, Not yet recruiting, Janssen Research & Development, LLC

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

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

P2, N=120, Not yet recruiting, Janssen Research & Development, LLC

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

P2, N=30, Not yet recruiting, Stanford University

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

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.

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

P2, N=450, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2026 --> Dec 2026

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

P1, N=38, Not yet recruiting, Thomas Martin, MD

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

P1, N=182, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Dec 2024 --> Jul 2025

P1, N=15, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Dec 2024 --> Aug 2024

P2, N=264, Recruiting, Celgene | Trial primary completion date: Dec 2023 --> Jul 2025

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

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

P2, N=450, Recruiting, Janssen Research & Development, LLC | N=320 --> 450

P1, N=152, Recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1

P1, N=15, Active, not recruiting, Janssen Pharmaceutical K.K. | Recruiting --> Active, not recruiting

P1, N=182, Recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1

P1, N=290, Active, not recruiting, Janssen Research & Development, LLC | Phase classification: P1b --> P1