Modakafusp alfa, a novel medicine, has shown early promise in treating multiple myeloma, a kind of bone marrow cancer, according to findings presented at the 2022 American Society of Hematology (ASH) Annual Meeting by scientists from the University of Pennsylvania’s Abramson Cancer Center.
Patients who received 1.5 milligrammes of modakafusp every four weeks as part of the Phase I/II multicenter study (NCT03215030) had a partial response, or a 50% decline in their malignancy. Patients in the study had had at least three rounds of prior therapy, and their condition had either relapsed or stopped responding to the earlier drug.
“We are excited by these findings and continue to be optimistic about the potential this treatment holds for patients with multiple myeloma,” said presenting author Dan Vogl, MD, an expert in blood cancers, medical director of the Clinical Research Unit at Penn Medicine’s Abramson Cancer Center, and an associate professor of Hematology-Oncology at the Perelman School of Medicine of 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 five years ago. We now see that a substantial number of patients benefit from modakafusp as a single agent, including patients whose myeloma has become resistant to other treatments, which is really impressive.”
A fusion protein called modakafusp (created by Takeda Pharmaceuticals) directs interferon, a pro-inflammatory hormone also used to treat viral infections and other malignancies, to cells that carry CD38 on their surface. CD38 is a marker found on myeloma cells as well as a number of immune cells.
In the United States, there are anticipated to be 12,640 fatalities from multiple myeloma in 2022, according to the American Cancer Society. Less than 1% of the population gets the cancer, making it rare.
Despite medical advancements, myeloma is presently incurable, and all patients experience malignant relapses following first chemotherapy and other initial lines of therapy. In this study, modakafusp showed promise in patients for whom other treatments targeting the same target, such as well-known monoclonal antibodies like daratumumab and isatuximab, had lost their efficacy. The study’s preliminary findings were presented at the ASH Annual Meeting in 2021. The medicine has tolerable side effects and induces potent anti-myeloma responses, according to the final safety and effectiveness studies released this year.
“Modakafusp 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,” Vogl said. “We also saw responses in patients whose myeloma had developed resistance to all currently available effective therapies.”
According to expectations for this substantially pre-treated group, the majority of trial participants (87%) had adverse events due to the therapy. Neutropenia, or a reduction in white blood cells, and thrombocytopenia, or a low blood platelet count, were the most frequent side effects among research participants. About one-third of patients also experienced minor side effects following the medication’s infusion. In order to determine the ideal dose of modakafusp and learn more about its efficacy in treating myeloma, Vogl and his colleagues are currently recruiting patients in a randomised phase II research.
