Tecvayli (teclistamab-cqyv)

We then summarize the clinical development and distinguishing features of currently approved BCMA-targeted modalities-CAR T-cell therapies (ide-cel, cilta-cel), bispecific T-cell engagers (teclistamab, elranatamab, linvoseltamab), and the antibody-drug conjugate (belantamab mafodotin)-highlighting their efficacy, toxicity profiles, and practical positioning in relapsed/refractory MM. Finally, we review emerging resistance mechanisms, including γ-secretase-driven sBCMA elevation, ligand-rich APRIL/BAFF niches, and therapy-induced TNFRSF17 lesions, ranging from biallelic deletions to epitope-altering missense mutations and in-frame deletions within the BCMA extracellular domain. These insights inform rational strategies such as γ-secretase inhibition, dual-target CAR T-cells and bispecific T-cell engagers.

P1, N=30, Not yet recruiting, National Cancer Institute (NCI)

P2, N=160, Recruiting, University of Heidelberg Medical Center | Trial completion date: Aug 2028 --> Sep 2029 | Trial primary completion date: Feb 2027 --> Sep 2028

P2, N=80, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Oct 2025 --> Jan 2026

IEC-HS is a rare but potentially fatal complication. Our disproportionality analysis identifies significant reporting signals for tisa-cel and cilta-cel. The high absolute number of cases observed for products like axi-cel appears to reflect high utilization rather than a disproportionate risk, underscoring the necessity of using statistical signal detection methods when interpreting spontaneous reports.

P4, N=15, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting | Trial completion date: Sep 2025 --> Oct 2026 | Trial primary completion date: Apr 2025 --> Jun 2026

P3, N=400, Not yet recruiting, Janssen Research & Development, LLC

P3, N=614, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

P2, N=50, Not yet recruiting, University of Arkansas | Initiation date: Oct 2025 --> Apr 2026

P2, N=75, Recruiting, SCRI Development Innovations, LLC | Trial completion date: Mar 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Aug 2027

For solid cancers, these comprise the antibody-drug-conjugate Mirvetuximab Soravtansine for platinum-resistant ovarian cancer, the monoclonal antibody Zolbetuximab for Claudin-18.2 positive gastric adenocarcinoma and the checkpoint inhibitor Tislelizumab for esophageal squamous cell carcinoma. For the treatment of relapsed or refractory hematologic B cell malignancies, the use of bispecific T cell engaging antibodies like the BCMA-CD3 targeting Teclistamab and CD20-CD3 targeting Glofitamab were approved by the EMA recently.Combinatorial approaches of conventional chemotherapy and checkpoint inhibitors for the treatment of cholangiocarcinoma, urothelial carcinoma and endometrial carcinoma received recent approval.A CD38 antibody-based bridging therapy for the treatment of newly diagnosed multiple myeloma and the Glofitamab-based approach in combination with Gemcitabine and Oxaliplatin for relapsed DLBCL are the latest additions for hematologic malignancies after promising clinical trials.The first T cell products for the treatment of solid cancers using either tumor-infiltrating lymphocytes or TCR-engineered peripheral blood T cells were approved by the FDA in 2024, for the treatment of advanced melanoma (Lifileucel) and synovial sarcoma (Afamitresgene autoleucel). To further expand the success of T cell products to solid tumors, promising preclinical studies suggest solutions to main obstacles, such as modular CAR T cells, targeting of two antigens simultaneously or generation of cytokine-secreting 4th generation CAR T cells.

P1/2, N=302, Active, not recruiting, Janssen Research & Development, LLC | Phase classification: P1 --> P1/2