ICML 2025 | A Phase I/II trial exploring tafasitamab plus lenalidomide in relapsed CNS lymphoma

So we are pursuing a phase one investigation of tafasitamab in combination with lenalidomide in patients with a relapsed/refractory primary and secondary CNS lymphoma at a single institution site. And this is the rationale for this is our prior studies we showed that lenalidomide is an active agent in this disease with CNS penetration has the capacity to penetrate CSF and is associated with an M1 phenotype in patients when the drug is working and may have a capacity to promote the efficacy of monoclonal antibodies such as rituximab or the anti-CD19 antibody tafasitamab. We’re interested in tafasitamab for two reasons. Number one, CD20, the target of rituximab, may be downmodulated via prior exposure to the anti-CD20 antibodies, which is our standard of care in patients’ upfront induction regimens. And number two, CD19 is a great target in lymphoma and there’s evidence that CD19 is ectopically expressed in the blood-brain barrier in cells called vascular pericytes. And for this reason, we tested the efficacy of tafasitamab in highly refractory patients off study and in all of the patients we’ve seen responses in lenalidomide or pomalidomide resistant patients. And one of these responders is a patient who was in remission several years later, who was previously refractory to ibrutinib, lenalidomide, pomalidomide, autologous stem cell transplant and radiation. For this reason, we’ve been motivated to activate this trial, to design and activate this trial with support from Insight and have demonstrated in the course of this phase one investigation that number one we see actually significant activity is particularly in patients who are lenalidomide naive. This is a phase one dose escalation study in which we’re using a fixed dose of tafasitamab using the normal schedule as well as three dose levels of lenalidomide which were reduced from our prior work and analysis of lenalidomide monotherapy showing that lenalidomide, each of the dose levels, penetrate CSF, 10 milligrams, 15 milligrams, and 20 milligrams, but the higher dose levels, there’s more toxicity. So we’re doing a very rigorous analysis of the safety and exploratory analysis of efficacy in approximately 15 to 20 patient study. And thus far we’ve seen, as I said, activity at both the 10 and, particularly the 15 milligram dose level, and some quite sustained responses in patients with lenalidomide who are lenalidomide naive of some patients responding longer than six months thus far although the data is quite early but most encouragingly we’re not seeing any unexpected side effects there’s only been one toxicity thus far that is likely related to the combination in a patient that was heavily treated but we have many patients that are tolerating the regimen well without neurotoxicity or infectious complications or other hematologic toxicities.

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