ASH 2024 | Modakafusp alfa for heavily pre-treated myeloma: results of a Phase II dose optimization trial

So, modakafusp alfa is a novel treatment that is showing really nice results in the Phase I portion and therefore we proceeded with the Phase II portion of the treatment. 

In the Phase I, we used 1.5 or 3 milligrams per kilogram dosing. For Phase II, we try to move that to fixed dosing based on average weight. So patients were randomized 1:1 to receive either 120 milligrams or 240 milligrams of modakafusp alfa. Modakafusp alfa has a unique CD38 epitope that also has an attached interferon, attenuated interferon moiety to it. The goal for it is to activate the innate immune system as well as the adaptive immune system as well. 

We enrolled about 146 patients between dose 120 and 240. And patients were pretty refractory to prior treatments. We have about half the patients were penta refractory. About 21 patients received CAR-T treatment before enrollment, and about a third of the patients got T-cell engagers as well, prior to enrollment. So those are a very refractory population. 

And we were able to show that the response rates were in the 30% range for the 120 milligrams cohort and up to 41% in the 240 cohort. And this translated to about four to five months of progression-free survival. Those results are very encouraging, especially when we consider that those patients have no other options prior to enrollment to this trial. Unfortunately, for business reasons, the trial sponsorship was stopped and we could not finish the full enrollment of the Phase II portion of this trial. However, I truly believe this drug works and it has potential in the future to add to the drugs that we have or the options that we have for patients with relapsed/refractory myeloma once we can finish the Phase II trial of this drug. 

And regarding the side effects, most of the side effects were hematological. I would point out thrombocytopenia was pretty common. Also we have seen a signal for increased cough. And across all subgroups with subset analysis, the drug showed equal efficacy, regardless of high-risk cytogenetics or prior treatments. I would point out that the overall response rate, even after CAR-T treatment was encouraging. And for patients before CAR-T treatment, those who did not receive prior CAR-T treatment before they got modakafusp alfa, the response rates were pretty solid. Overall, the response rates for this drug were higher than the response rates that were initially reported with prior FDA-approved drugs. And that’s where we think that this drug will still have a future once we can pick up its Phase II trial and get it through the finish line.

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