ASH 2024 | Phase II trial of durvalumab + lenalidomide vs single-agent durvalumab in refractory/advanced CTCL

So we completed a Phase II study, single agent durvalumab, which is anti-PD-L1 inhibitor versus the combination of durvalumab plus lenalidomide. Each arm had patients with mycosis fungoides, Sézary syndrome stage 1B to 4A2. And each arm contained 12 patients. Actually in the combination we had 13 patients because one patient dropped out early and was not eligible for response assessment. 

So we’re very excited. The combination is actually really superior to the single agent and it has actually caused response rates that are higher than we’ve ever actually seen within standard of care in CTCL. And about two-thirds of the patients had actually responded. We had four patients with complete responses and five partial responders among those 12 patients eligible for response, versus in the single agent arm there were only five patients with partial responses but no complete responses. In addition, two patients with durvalumab alone actually got worse or progressed while on treatment. So on average patients had a treatment of six cycles, six, seven cycles. The minimum cycle was three months when we recorded responses. 

We have seen in terms of toxicities, which is mostly grade 1 and grade 2, a little more in the combination arm, likely due to the combination with lenalidomide. Fatigue was more common, also hematologic toxicities, but very mild decrease in neutrophils and white cells. In terms of immune-related adverse events, tumor flare was the most common in both arms, so more common, however, in the combination arm and some symptoms such as diarrhea. Actually, one quarter of the patients in each arm developed thyroid dysfunction, which is likely related to durvalumab, and actually is similar to what’s reported in other trials in other tumors. 

So we assessed actually the tumor microenvironment. So our preliminary results actually show that actually the combination can shut down the cell-cell communication of immunosuppressive cells with the tumor cells and actually increase also the CD8 and NK cells that actually had communicated actually or cytotoxic effects on the tumor cells. So it’s very exciting. The tumor cells also decreased significantly while we didn’t see much changes really in the single agent arm. 

PD-L1 expression, we looked in both arms, the expression level didn’t matter for response so far, but we knew actually the combination, it decreased the expression levels of PD-L1 while in the single agent we didn’t see that. I forgot actually to mention the progression-free survival was 8.5 months in the single arm and in the combination arm it was not reached so it’s actually very exciting.

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