Seagen (NASDAQ: SGEN), currently in the process of being acquired by Pfizer (NYSE: PFE), has released the results of a Phase II study combining its antibody drug conjugate (ADC) Adcetris (brentuximab vedotin) with Merck, Sharp & Dohme’s (MSD; NYSE: MRK) anti-PD-1 therapy Keytruda (pembrolizumab). The study focused on patients with primary resistant or secondary refractory melanoma or non-small cell lung cancer (NSCLC) who had previously received anti-PD-1 treatment.
Study Results and Objective Response Rates
The objective response rates (ORR) for the study were as follows: primary melanoma at 18%, secondary melanoma at 22%, primary NSCLC at 8%, and secondary NSCLC at 14%. Disease control rates (DCR) were 71%, 80%, 67%, and 72% respectively. These results indicate the potential efficacy of the combination therapy in treating these patient populations.
CD8 T-Cell Infiltration and Re-sensitization Potential
Notably, the study observed CD8 T-cell infiltration in the tumor microenvironment of responding patients, suggesting a potential for re-sensitization to PD-1 inhibitors. This finding is significant as it may indicate a renewed response to PD-1 therapies in patients who had previously shown resistance or refractoriness.
Expansion of Trial and Future Directions
Building on these encouraging results, Seagen plans to extend the trial to include first-line NSCLC and head and neck cancer, broadening the potential applications of the combination therapy.
Pre-clinical Evidence for SGN-35T
In addition to the clinical study results, Seagen announced pre-clinical evidence for its CD30-directed ADC candidate, SGN-35T. The compound has shown cytotoxic effects on CD30-expressing tumor cells and regulatory T-cells but not on CD8-expressing T-cells. This suggests that SGN-35T may offer a similar efficacy profile to Adcetris with improved tolerability, expanding the range of treatment options for patients with CD30-expressing malignancies.-Fineline Info & Tech
