ICML 2025 | The PRiZM+ platform study for R/R primary CNS lymphoma: first results with zanubrutinib monotherapy

So patients with relapsed/refractory primary CNS lymphoma are a really difficult group of patients. They have poor prognosis, there’s no standard of care and there are no approved therapies in the US, EU or UK. So this is a really big unmet need. So we’ve designed the PRiZM+ Phase II platform study to investigate novel therapies in this difficult patient group, and I’m presenting the primary analysis of the first cohort at the ICML conference here in Lugano. The overall response rate which was the primary endpoint, 55% by central review, which was quite concordant with local investigator judgment of the response rate, And then when we look further at the data the CR rate by central review 35% which is quite a high bar in primary CNS lymphoma, and that’s particularly important when we think about the characteristics of patients. So patients included ECOG performance status two and three. Nearly half of patients had had a prior autologous stem cell transplant with thiotepa conditioning. It’s representing a very much chemotherapy resistant group. And an important aspect of the study was to include patients who had neurocognitive dysfunction so they were unable to provide informed consent and there’s a legal mechanism where we could enroll those patients who would previously be not enrolled in clinical trials. So a quarter of the patients in our cohort one of the PRiZM+ study with zanubrutinib monotherapy fell within that group. 

So we have the overall response data, the CR rates, and then we look at the progression-free survival, really impressive in this patient group, an overall survival of approximately a year. And we still have five patients on zanubrutinib monotherapy at the last data cut. 

Looking ahead, we have plans to move within the platform designed to cohort two with a novel triplet of zanubrutinib, tafasitamab and lenalidomide, and this is the first time this combination has been used in any type of lymphoma and I think it represents a potential step change, at least for patients who have access to the trial within the UK.

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