A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma

Modakafusp alfa is a first-in-class immunocytokine-directing interferon alfa to CD38+ cells. Our previous phase 1/2 trial identified 2 potential phase 2 doses of modakafusp alfa for patients with relapsed/refractory multiple myeloma (RRMM): 1.5 or 3 mg/kg every 4 weeks. The overall response rate (ORR) among 30 patients treated at 1.5 mg/kg was 43%. This phase 2 dose optimization study randomized 147 patients with triple-class refractory disease and ≥3 previous lines of therapy 1:1 to modakafusp alfa 120 mg (n = 71) or 240 mg (n = 75) every 4 weeks (fixed-dose equivalents of 1.5 and 3 mg/kg every 4 weeks). Patients had received a median of 6 previous lines of therapy; 66% were penta-exposed and 45% had previously been exposed to anti-B-cell maturation antigen (BCMA) therapy. Modakafusp alfa development was discontinued for strategic reasons by the sponsor and the study was terminated early. At median follow-up of 7.3 and 7.6 months in the 120- and 240-mg arms, ORRs were 32% and 41%, and median progression-free survival was 4.1 and 5.3 months, respectively. ORRs were higher in patients who had not received previous BCMA therapy (46% vs 29%). The most common treatment-related adverse events (TEAEs) in the 120- and 240-mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%; respectively) and neutropenia (68% and 73%; grade ≥3, 56% and 68%; respectively); 90% and 96% of patients, respectively, experienced grade ≥3 TEAEs; 39% and 44%, respectively, experienced serious TEAEs. Our results confirm the efficacy of single-agent modakafusp alfa for patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT03215030.

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Publication Details

Journal
Blood
Published
2025-04-25
DOI
https://doi.org/10.1182/blood.2024027873
Citations
2
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
3.54

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article

A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma

Moshe E. Gatt, Sarah A. Holstein, Xavier Parot, Meletios Α. Dimopoulos et al.
2 citations
Blood
Multiple Myeloma Research and Treatments
3.54
article

A phase 2 randomized study of modakafusp alfa as a single agent for patients with relapsed/refractory multiple myeloma

Moshe E. Gatt, Sarah A. Holstein, Xavier Parot, Meletios Α. Dimopoulos, Hila Magen, Salomon Manier, Cheryl Li, Dan T. Vogl, Shebli Atrash, Nishi Shah, Omar Nadeem, Hira S. Mian, Cyrille Touzeau, Patrick M. Travis, Kaveri Suryanarayan, Fredrik Schjesvold, Meral Beksaç, Christian Burris Gocke, Rakesh Popat, Laurent Frenzel, Shuli Li, Dasha Cherepanov, Allison Nelson
article en
2 citations

Abstract

Modakafusp alfa is a first-in-class immunocytokine-directing interferon alfa to CD38+ cells. Our previous phase 1/2 trial identified 2 potential phase 2 doses of modakafusp alfa for patients with relapsed/refractory multiple myeloma (RRMM): 1.5 or 3 mg/kg every 4 weeks. The overall response rate (ORR) among 30 patients treated at 1.5 mg/kg was 43%. This phase 2 dose optimization study randomized 147 patients with triple-class refractory disease and ≥3 previous lines of therapy 1:1 to modakafusp alfa 120 mg (n = 71) or 240 mg (n = 75) every 4 weeks (fixed-dose equivalents of 1.5 and 3 mg/kg every 4 weeks). Patients had received a median of 6 previous lines of therapy; 66% were penta-exposed and 45% had previously been exposed to anti-B-cell maturation antigen (BCMA) therapy. Modakafusp alfa development was discontinued for strategic reasons by the sponsor and the study was terminated early. At median follow-up of 7.3 and 7.6 months in the 120- and 240-mg arms, ORRs were 32% and 41%, and median progression-free survival was 4.1 and 5.3 months, respectively. ORRs were higher in patients who had not received previous BCMA therapy (46% vs 29%). The most common treatment-related adverse events (TEAEs) in the 120- and 240-mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%; respectively) and neutropenia (68% and 73%; grade ≥3, 56% and 68%; respectively); 90% and 96% of patients, respectively, experienced grade ≥3 TEAEs; 39% and 44%, respectively, experienced serious TEAEs. Our results confirm the efficacy of single-agent modakafusp alfa for patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT03215030.

BloodVol. 146(9)
Oslo University Hospital (NO), Hôpital Necker-Enfants Malades (FR), University College Hospital (GB), Centre National de la Recherche Scientifique (FR), Albert Einstein College of Medicine (US), Nebraska Medical Center (US), Montefiore Medical Center (US), University College London Hospitals NHS Foundation Trust (GB), Johns Hopkins University (US), Inserm (FR), Hebrew University of Jerusalem (IL), Korea University (KR), National and Kapodistrian University of Athens (GR), Université de Lille (FR), Sheba Medical Center (IL), Johns Hopkins Medicine (US), Hadassah Medical Center (IL), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Lille’s Cardiology Hospital (FR), Quantitative BioSciences (US), Levine Cancer Institute (US), Highlands Oncology Group (US), Dana-Farber Cancer Institute (US), Istinye University (TR), Takeda (United States) (US), Hospital Estadual Centra (BR), Liv Hospital (TR), Korea University (JP), University College London (GB), University of Nebraska Medical Center (US), University of Pennsylvania (US), McMaster University (CA)
Amgen, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Celgene, Takeda Pharmaceuticals U.S.A., Regeneron Pharmaceuticals, BeiGene, Active Biotech, Genentech
Good health and well-being
Openalex Percentile: Top 8%
Multiple Myeloma Research and Treatments
3.54
DOIOpen Access PDFOpenAlex
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