P2, N=20, Not yet recruiting, Stanford University | N=30 --> 20

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

P1/2, N=316, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jun 2027 --> Apr 2025

We report a 63-year-old male who received ciltacabtagene autoleucel CAR T cells and the GPRC5D × CD3 bispecific talquetamab for early relapse of his multiple myeloma...These expanded clones exhibited an exhausted effector-memory T cell transcriptional signature, and the neoplasm itself was sensitive to dexamethasone treatment...Before and after CAR T whole-genome analyses implicated clonal outgrowth of a TET2-mutated precursor propelled by additional subclone-specific loss of heterozygosity and other secondary mechanisms. This case highlights the evolution of a CAR-carrying peripheral T cell lymphoma following CAR T cell and bispecific T cell engager therapy, offering critical insights into the clonal evolution from a predisposed hematopoietic precursor to a mature neoplasm.

P2, N=130, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2027 --> Oct 2027

P2, N=23, Not yet recruiting, Larysa Sanchez

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

P2, N=30, Not yet recruiting, Stanford University | Initiation date: Nov 2024 --> Nov 2025 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=30, Recruiting, Janssen Research & Development, LLC | Trial completion date: Feb 2027 --> Aug 2026

P1, N=100, Recruiting, Janssen Research & Development, LLC

P1, N=166, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2025 --> Apr 2027 | Trial primary completion date: Jul 2025 --> Mar 2025

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

P1, N=82, Recruiting, Sanofi | Phase classification: P1/2 --> P1

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

P2, N=130, Recruiting, Janssen Research & Development, LLC | Active, not recruiting --> Recruiting

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.

P1, N=136, Recruiting, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=225, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=480 --> 225 | Trial completion date: Aug 2026 --> Feb 2026 | Trial primary completion date: Aug 2026 --> Feb 2026

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

P1/2, N=316, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Jun 2027 --> Apr 2025 | Recruiting --> Active, not recruiting

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=136, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.

P1/2, N=82, Recruiting, Sanofi | Not yet recruiting --> Recruiting | Phase classification: P1 --> P1/2

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.

Forimtamig is currently being evaluated in Phase 1 clinical trials in relapsed and refractory myeloma (RRMM) patients for monotherapy and in combination treatments. NCT04557150.

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

P1, N=180, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2026 --> Apr 2027

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.

P1/2, N=116, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting | Initiation date: Feb 2024 --> Jul 2024

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