EHA 2025 | Phase I trial of SGN-35C, a novel CD30-directed antibody-drug conjugate, in R/R lymphomas

So on behalf of my co-authors, I had the privilege of presenting results for my first in-human phase one trial of SGN-35C at EHA. So SGN-35C, it’s a novel CD30-directed antibody drug conjugate. It shares the same antibody backbone as brentuximab, but it’s conjugated to a camptothecin-derived topoisomerase 1 inhibitor. And this unique payload represents a mechanistically distinct approach compared to the more traditional MMAE ADCs with preclinical data with this compound demonstrating cytotoxicity even in BV-resistant cell lines. And so the study that I presented, it’s ongoing. It’s enrolling adults with relapsed or refractory CD30 positive lymphomas, including classical Hodgkin lymphoma, peripheral T-cell lymphoma, as well as diffuse large B-cell lymphoma. It is given intravenously every three weeks. It follows a standard three plus three dose escalation design, and dose level one started at 0.6 milligrams per kilogram. And at the time of data cut off at EHA, 35 patients had initiated therapy. 22 had classical Hodgkin lymphoma, nine with peripheral T-cell lymphoma and four with DLBCL. The median age was about 40 years, and it was a heavily pretreated population. So the median number of prior lines of therapy was five. 91% or the vast majority of patients had received prior BV and then the vast majority of the Hodgkin lymphoma patients had also received prior PD-1 therapy as well. And currently with the dose escalation SGN-35C is now being evaluated at dose level 4 and in regards to the safety profile we’ve seen so far from dose levels 1 to 4, it’s been generally very well tolerated. Most common treatment-related AEs were nausea, anemia, alopecia, and fatigue, majority being grade 1 and 2. There was one DLT, a grade 3 thrombocytopenia, was reported at dose level two or three, essentially. But there were no grade 3 AEs, no treatment discontinuations due to toxicity were observed. And more encouragingly, the preliminary efficacy data looks very promising as well. So overall response rate was 70% in this heavily pretreated population, including an 11% CR rate. In terms of overall response rates by subgroup, it was 76% in Hodgkin lymphoma, 63% in peripheral T-cell lymphoma, and 50% in DLBCL. Responses were observed across all doses, even at the lowest dose levels. And at a median follow-up of three months, 77% of patients still remained on treatment with one discontinuation due to proceeding to an allotransplant. So, you know, clinically, I think these results are very promising. You know, as we all know, patients who have relapsed/refractory CD30 positive lymphomas, particularly ones who have progressed after brentuximab and in classical Hodgkin lymphoma, especially those who have progressed after both BV and checkpoint inhibitors, they really face, you know, a lack of effective treatment options. And even in patients who actually initially responded to BV, you know, there is cumulative toxicity in terms of peripheral neuropathy that can limit its long-term use. And so SGN-35C with its novel mechanism and favorable safety profile shows early signs of clinical activity, even in heavily pretreated patients and highly refractory populations. So I think it does represent a promising therapeutic option, especially for patients who have BV refractory disease. More importantly, I think the tolerability observed to date does support potential future developments in terms of combination strategies or even treatment in earlier lines of therapy. Me and the investigators, we all look forward to really defining what is the recommended phase two dose and then moving on to evaluating, you know, more in detail efficacy in terms of durability of responses and clarifying, you know, its role in kind of the broader CD30 positive lymphomas.

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