225Ac-daratumumab / Actinium Pharmaceuticals - LARVOL DELTA

A Phase 1 Trial of 225Actinium-DOTA-Daratumumab in Patients with Daratumumab-refractory Multiple Myeloma: Results from First Cohorts (IMW 2024) - "Introduction: Studies from our institution demonstrated that CD38 remains expressed and targetable in Dara-refractory MM (Viola et al. 225Ac-Dara in Dara-refractory MM is a novel strategy to circumvent immune exhaustion and repurpose CD38-targeting. Our phase 1 study is ongoing with primarily hematologic toxicity observed. Several patients had stable disease after a single dose."

Clinical • IO biomarker • P1 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

First-in-human trial of 225Actinium-DOTA-daratumumab, an alpha-emitting radioimmunotherapy, in patients with daratumumab-refractory multiple myeloma (AACR 2026) - "Purpose: Given that most patients with multiple myeloma (MM) become refractory to daratumumab (Dara) but retain CD38 expression, we developed a CD38-targeting radioimmunotherapy (RIT) by conjugating the α emitter actinium-225 to Dara using a DOTA chelator (225Ac-Dara). We conducted a first-in-human trial of 225Ac-Dara co-infused with the imaging agent 111Indium-DOTA-Dara (111In-Dara). 225Ac-Dara in Dara-refractory MM is a novel strategy to circumvent immune exhaustion and repurpose CD38-targeting. Repeated administration of lower doses may improve the therapeutic window and duration. Translational and clinical observations from this trial support possible synergy between 225Ac-Dara and subsequent immunotherapies."

Clinical • First-in-human • IO biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • SDC1

Anti-CD38 targeted radiation is effective and enhances CAR-T cell recruitment and expansion in resistant extramedullary multiple myeloma (ASH 2025) - "EMD currently poses a significant challenge to MM treatmentbecause of its aggressive nature and resistance to current therapies, including the anti-CD38 antibodydaratumumab (Dara) and CAR-T cells...Notably, these relapsed mice show noMM engraftment in the BM and exhibit limited immune infiltration in EMD tumors, supporting the role oftumor localization in therapeutic resistance.To investigate if CD38 remains a viable targetable in EMD, independently of immune system engagement,we conjugated Dara to the alpha-emitting radionuclide Actinium-225 (225Ac-Dara) as a targetedradionuclide therapy (TRT) toward CD38-expressing cancer cells...Moreover, the TRT–pretreated mice had significantlyhigher tumor necrosis when compared to the other treatment groups.In sum, we report for the first time that CD38-TRT not only provides therapeutic benefit in immune-resistant EMD but also enhances CAR-T cell infiltration and expansion within these tumors. These findingssuggest that CD38-TRT..."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Leukemia • Multiple Myeloma