P1, N=9, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 9

P3, N=520, Not yet recruiting, GlaxoSmithKline

Background : High dose melphalan and ASCT, followed by lenalidomide (len) maintenance, improves progression-free survival (PFS) in MM but is generally not curative. Conclusions : In newly-diagnosed MM patients with <CR after induction, belamaf every 3 months in conjunction with ASCT and len maintenance appears feasible (at 1.9 mg/kg starting dose), with expected reversible ocular toxicities, and so far has promising rates of sCR, MRD-negativity, and PFS. Accrual and follow-up are ongoing.

P2, N=221, Completed, GlaxoSmithKline | Active, not recruiting --> Completed

P1/2, N=4, Terminated, GlaxoSmithKline

P1/2, N=70, Active, not recruiting, Wake Forest University Health Sciences | Trial completion date: Oct 2024 --> Nov 2032 | Trial primary completion date: Oct 2024 --> Apr 2029

We report enhanced cytotoxic activity in the presence of high levels of sBCMA compared to a belantamab mafodotin biosimilar (J6M0-mcMMAF)...In Cynomolgus monkeys, STI-8811 was well tolerated, with toxicities consistent with other BCMA targeting ADCs with auristatin payloads in clinical studies. STI-8811 has the potential to outperform current clinical candidates with lower toxicity and higher activity under conditions found in patients with advanced disease.

P2, N=35, Active, not recruiting, Stichting European Myeloma Network | Recruiting --> Active, not recruiting

P1, N=47, Terminated, Celgene | N=160 --> 47 | Active, not recruiting --> Terminated; Slow accrual

P=N/A, N=78, Completed, Fondazione EMN Italy Onlus | Recruiting --> Completed | Trial completion date: Dec 2024 --> Aug 2024

P2, N=34, Recruiting, Emory University | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=1, Terminated, Medical College of Wisconsin | N=45 --> 1 | Trial completion date: Jan 2032 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Jan 2024; Low enrollment.

P1/2, N=120, Active, not recruiting, Canadian Myeloma Research Group | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P1/2, N=78, Recruiting, Heidelberg Pharma AG | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: Aug 2024 --> Aug 2025

P1/2, N=70, Active, not recruiting, Wake Forest University Health Sciences | Recruiting --> Active, not recruiting

Deliberate consideration of treatment timing, preserving T-cell health, overcoming antigenic loss, and comprehension of the complex tumor microenvironment would be key to maximizing therapeutic benefits and minimizing adverse effects. This review summarizes novel targets in development for myeloma beyond BCMA, presenting pivotal safety and efficacy data derived from clinical trials where available and the considerations vital for navigating this expanding landscape of immunotherapeutic options.

P2, N=177, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Feb 2025 | Trial primary completion date: May 2024 --> Aug 2024

P1/2, N=88, Not yet recruiting, Alliance for Clinical Trials in Oncology | Initiation date: Mar 2024 --> Aug 2024

P1/2, N=153, Completed, GlaxoSmithKline | Active, not recruiting --> Completed

P1, N=144, Recruiting, GlaxoSmithKline | Trial completion date: Nov 2025 --> Jun 2025 | Trial primary completion date: Apr 2025 --> Nov 2024

P3, N=357, Recruiting, GlaxoSmithKline | Trial primary completion date: Sep 2024 --> Jan 2024

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.

P1/2, N=68, Active, not recruiting, Australasian Myeloma Research Consortium | Recruiting --> Active, not recruiting

P2, N=33, Not yet recruiting, Cristiana Costa Chase, DO | Initiation date: Mar 2024 --> Jun 2024

P1/2, N=5, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Mar 2024 | Trial primary completion date: May 2025 --> Mar 2024

P1/2, N=10, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting | N=64 --> 10 | Trial primary completion date: Mar 2024 --> Jun 2023

P1/2, N=37, Recruiting, University of Texas Southwestern Medical Center | Not yet recruiting --> Recruiting

P2, N=20, Recruiting, Roswell Park Cancer Institute | Trial completion date: Feb 2026 --> Sep 2026 | Trial primary completion date: Feb 2026 --> Sep 2026

Bispecific antibodies offer superior efficacy and tolerability compared to ADCs, but prolonged exposure causes significant cumulative infectious risk. In this review, we will examine the role of BCMA in MM biology, the approved and emerging therapies targeting this antigen, and how these agents can be optimally sequenced.

P2, N=50, Not yet recruiting, Massachusetts General Hospital | Initiation date: Nov 2023 --> Jun 2024

P1, N=160, Active, not recruiting, Celgene | Trial completion date: May 2025 --> Aug 2024 | Trial primary completion date: May 2025 --> Aug 2024

P1/2, N=88, Not yet recruiting, Alliance for Clinical Trials in Oncology

P2, N=33, Not yet recruiting, Cristiana Costa Chase, DO | Initiation date: Nov 2023 --> Mar 2024

P1, N=160, Active, not recruiting, Celgene | Trial completion date: Apr 2024 --> May 2025 | Trial primary completion date: Apr 2024 --> May 2025

P2, N=221, Active, not recruiting, GlaxoSmithKline | Trial completion date: Aug 2023 --> Jul 2024

P1/2, N=24, Recruiting, Yale University

P=N/A, N=30, Completed, Duke University | Enrolling by invitation --> Completed

P1/2, N=9, Terminated, GlaxoSmithKline

We explored BCMA as a novel target for immunotherapy for AML as high levels of BCMA are found on the surfaces of AML cells. We illustrated proof of concept of BCMA directed therapy via TCE therapy both in vitro and in vivo. Thus, BCMA should be considered a promising target for immunotherapy of AML including TCEs, CAR based or antibody drug conjugate approaches.

Median time since diagnosis was 9 years with a median of 5 prior therapies (range: 4- 7) including Auto-SCT (n=7), Allo-SCT (n=1); all patients had received lenalidomide, pomalidomide, bortezomib, carfilzomib & daratumumab, 2 patients had BCMA CAR T cell therapy. The RP2D of BelCyd is 2. 5 mg/kg Q6W plus Cy 500 mg & dexa 40mg; no new safety signal was seen. BelCyd activate NK, cytotoxic T cells & macrophages adding to Bel direct MM cytotoxicity.

The Phase 3 DREAMM-3 trial (NCT04162210) evaluated single-agent belamaf vs. pomalidomide plus low-dose dexamethasone in patients with RRMM at second relapse or later (Weisel et al. PopPK and E-R analyses for DREAMM-3 demonstrated the impact of disease factors and patient characteristics on PK, efficacy, and safety endpoints following single-agent belamaf, consistent with prior results for later-line populations.

P1/2, N=36, Recruiting, Hellenic Society of Hematology | Not yet recruiting --> Recruiting