ASH 2023 | Phase I trial of the menin inhibitor JNJ-75276617 in patients with acute leukemia

A very exciting time today in AML and ALL, especially in patients with KMT2A and NPM1 mutant disease. When they relapse, they have nothing available, and the outcome is very poor. We’re able to understand the physiopathology of the disease, and we came up with menin inhibitors -one of them is JNJ-6617. And what I showed at ASH is the first human trial, it’s a Phase I study in 86 patients who have failed multiple lines of therapy before. We tested the inhibitors with optimizing the dose of the drug, and what you’ve seen so far is around 50% response rate, which is unheard of in patients who have failed multiple agents. And so far, we’ve seen responses being durable, 6.5 months and onward, which is quite encouraging. We’re still expanding on this until we get the recommended phase two dose, and hopefully after that expand. It’s the first trial and I think it’s a really great start. The drug is effective, and from a safety point of view, we’ve seen what they call differentiation syndrome, which is one of the most common DLTs. However, we’re able to mitigate that by going to a twice-daily dose and a step-up dosing approach, and that took care of the concerns. And something of great importance, we’ve seen no QT prolongation, except for one case, and usually not so myelosuppressive because patients receiving treatment are still not having a low count. And in fact, half of the responders are maintaining the remission beyond six months and onward. So, very encouraging data and with this data as well, we have a combination trial ongoing with promising results so far.