The novel drug modakafusp alfa has shown early promise in combating relapsed/refractory multiple myeloma, according to new findings presented by Vogl et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 565).
Background
Modakafusp alfa is a fusion protein that targets interferon—the pro-inflammatory hormone used to treat viral infections and other cancers—to cells that have the surface marker CD38.
According to the American Cancer Society, about 12,640 deaths from multiple myeloma are expected to occur in the United States in 2022. Affecting less than 1% of the population, multiple myeloma is uncommon but is not curable—and despite advances in treatment, all patients experience relapses after initial treatment and other early lines of therapy.
Study Methods and Results
In the new study, researchers discovered that among the patients in the phase I/II multicenter trial (ClinicalTrials.gov identifier NCT03215030) receiving 1.5 mg of modakafusp alfa every 4 weeks, 43% of them saw a partial response. Patients enrolled in the study had received at least three prior lines of treatment, and experienced relapsed disease or stopped responding to previous treatments before undergoing the regimen of modakafusp alfa.
“We are excited by these findings and continue to be optimistic about the potential this treatment holds for patients with multiple myeloma,” said lead study author Dan T. Vogl, MD, Associate Professor of Hematology-Oncology at the Hospital of the University of Pennsylvania and Medical Director of the Abramson Cancer Center Clinical Research Unit at the Perelman School of Medicine at the University of Pennsylvania. “We have been working with this new medication at Penn since we gave it to the first patient ever to receive it 5 years ago. We now see that a substantial number of patients benefit from modakafusp [alfa] as a single agent, including patients whose myeloma has become resistant to other treatments, which is really impressive.”
In this trial, modakafusp alfa made a positive difference in patients for whom drugs aimed at the same target—including well-established monoclonal antibodies like daratumumab and isatuximab—were no longer effective.
Preliminary results from the study, published by Vogl et al in Blood, were presented during the 2021 ASH Annual Meeting and Exposition—and the final safety and efficacy results presented this year confirmed that modakafusp alfa caused manageable side effects and produced strong antimyeloma responses.
The researchers revealed that among the patients involved in the study, 87% of them experienced treatment-related adverse events—as expected for this pretreatment-dominant population. The most common side effects among study participants included neutropenia and thrombocytopenia, and about one-third of patients had mild reactions after infusion of the medication.
Conclusions
“Modakafusp [alfa] has a truly novel mechanism of action, delivering a hormonal signal directly to target cells that simultaneously is toxic to cancer cells while stimulating an immune response. We saw responses in patients whose cancer did not respond to or who experienced a relapse after receiving the anti-CD38 antibody drugs that are currently on the market,” Dr. Vogl emphasized. “We also saw responses in patients whose myeloma had developed resistance to all currently available effective therapies.”
Dr. Vogl and his colleagues hope to identify the optimal dose of modakafusp alfa and provide more information about its effectiveness in patients with relapsed/refractory myeloma in a future randomized phase II trial.
Disclosure: The research in this study was sponsored by Takeda Pharmaceuticals. For full disclosures of the study authors, visit ash.confex.com.
