Seagen highlights first solid tumor data for ADCETRIS combination

Seagen announced the first presentation of data evaluating ADCETRIS in combination with an anti-PD-1 checkpoint inhibitor in non-small cell lung cancer and melanoma, and shared preclinical data for an investigational CD30-directed antibody-drug conjugate that uses a novel tripeptide linker. The studies were presented at the Society for Immunotherapy of Cancer 38th Annual Meeting, taking place November 3-5, 2023, in San Diego. The Phase 2 trial SGN35-033 explored the combination of ADCETRIS with pembrolizumab in 55 patients with non-small cell lung cancer and 58 patients with melanoma who either had no response to previous anti-PD-1 treatment or who experienced cancer progression after initial response to anti-PD-1 therapy. NSCLC cohorts were evaluated using RECIST v1.1 and melanoma cohorts were evaluated using immune RECIST. In NSCLC, the ADCETRIS and pembrolizumab combination demonstrated an objective response rate of 8% and 14% in patients with primary and secondary refractory NSCLC, respectively. Disease control rates – inclusive of complete responses, partial responses and stable disease – were 67%. In melanoma, the ADCETRIS and pembrolizumab combination demonstrated an ORR of 18% and 22%, in primary and secondary refractory metastatic cutaneous melanoma, respectively. DCRs were 71% and 80%, respectively. The study design included melanoma patients who were treated in the study within 90 days of receiving prior anti-PD-1 therapy. The safety profile of ADCETRIS was consistent with previous studies, and no new safety signals were observed. Increased CD8 T cell infiltration was observed in the tumor microenvironment of patients who responded to the combination treatment, suggesting potential re-sensitization to PD-1 inhibitors. The study is currently enrolling patients in previously untreated NSCLC and head and neck cancer. SGN-35T is a next generation CD30-directed ADC that uses a novel tripeptide linker designed to preferentially release its cytotoxic payload in tumor cells to limit off-target toxicity. Preclinical data suggest that SGN-35T may be highly effective, like ADCETRIS, with the potential for improved tolerability. SGN-35T is an investigational agent, and its safety and efficacy have not been established. In this in vitro study, SGN-35T was cytotoxic to CD30-expressing tumor cells and CD30-expressing regulatory T cells, whereas CD8-expressing T cells were unaffected by SGN-35T. The observations support future clinical investigation of SGN-35T in solid tumors.