Optimizing Modakafusp Alfa for Relapsed/Refractory Multiple Myeloma | Shebli Atrash, MD | #ASH24

This is Shebli Atrash from the Levine Cancer Institute, Charlotte, North Carolina. I will be presenting the results from the optimization of modakafusp alfa in patients with relapsed refractory multiple myeloma.

Modakafusp alfa is an attenuated anti-CD38, attenuated interferon alfa moiety attached to anti-CD38 monoclonal antibody. The drug aims at activating the adaptive and innate immune system to fight multiple myeloma.

We recently published the results of a phase 1 trial. In that trial, we identified two doses of interest to proceed with phase 2: 3mg/kg and 1.5mg/kg, which translates to 120mg, a fixed dose, or 240mg fixed dose of modakafusp alfa, which was used for the randomization for phase 2.

The trial was randomized 1 to 1. The primary endpoint was overall response rate. So in terms of overall response rates, we have patients who were enrolled, penta-refractory, and enriched penta-refractory patients. A lot of patients had progression even after CAR-T, BCMA CAR-T treatments. So those are populations that have unmet needs and with no other options available as standard of care.

In terms of response in the 120mg arm, we showed response rates close to 30%, and in the 240mg arm, the overall response rate is about 40%, a little bit above 40%. The drug was effective. Most of the significant side effects were related to hematological side effects, very manageable. Most significantly, was thrombocytopenia, and non-hematological side effects were fatigue and mild cough. But overall, there was not a big signal for infections, especially in those patients with a new surge of immune therapies, where infections are becoming more of a highlight for those patients who get BCMA treatments. With this drug, we did not see many infections.

In terms of subset analysis, the drug showed an overall response rate of a little bit less than 30% for patients after CAR-T, BCMA, and the same thing for patients with penta-refractory disease. We enrolled a total of 146 patients, so a little bit more than 70 patients in each arm.

The overall conclusion from the trial is that the drug is effective and shows an early signal of response. However, we could not finish the trial as the funding was stopped for business reasons. We look forward to future trials on this drug that could carry it forward and cross the finish line for FDA approvals.