Blenrep (belantamab mafodotin-blmf)

P1, N=48, Recruiting, GlaxoSmithKline | N=124 --> 48 | Trial completion date: Feb 2028 --> Sep 2028 | Trial primary completion date: Sep 2027 --> Sep 2028

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. 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

P1/2, N=258, Recruiting, Sanofi | N=197 --> 258

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.

P1/2, N=300, Recruiting, Karyopharm Therapeutics Inc | Active, not recruiting --> Recruiting

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

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=70, Active, not recruiting, Wake Forest University Health Sciences | Recruiting --> Active, not recruiting

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=197, Recruiting, Sanofi | Trial completion date: Dec 2027 --> Mar 2028 | Trial primary completion date: Dec 2027 --> Jun 2027

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=300, Active, not recruiting, Karyopharm Therapeutics Inc | Phase classification: P1b/2 --> P1/2 | N=518 --> 300 | Trial completion date: Jan 2025 --> Apr 2027 | Trial primary completion date: Jan 2025 --> Apr 2027

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

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

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

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

P1, N=124, Recruiting, GlaxoSmithKline | Not yet recruiting --> Recruiting | Phase classification: P1/2 --> P1 | Trial completion date: Jun 2027 --> Feb 2028 | Initiation date: Feb 2023 --> Jun 2023 | Trial primary completion date: Jun 2027 --> Sep 2027

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

P1/2, N=197, Recruiting, Sanofi | N=123 --> 197 | Trial completion date: Nov 2028 --> Dec 2027 | Trial primary completion date: Nov 2028 --> Dec 2027

P1/2, N=9, Terminated, GlaxoSmithKline

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.

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.

A single dose of CAR2 Anti-CD38 CAR-T cells was administered 2 days post lymphodepletion with single-agent cyclophosphamide 1. This phase I trial demonstrated that CAR2 anti-CD38 A2 CAR-T cells were generally well tolerated at the Cohort 2 (MTD) dose and demonstrated objective though short responses even in patients progressing after daratumumab and belantamab mafodotin. More clinical studies are needed to optimize the efficacy and tolerability of CAR-T cell therapies for patients with RRMM. This study was completed, and no more patients will be enrolled.