Response: Response rates to PD-1/PD-L1 blockade in solid tumors are reported at 10-20%. Remarkably, response rates of 65% to 87% have been reported in patients with refractory classical Hodgkin lymphoma treated with checkpoint inhibitors.
In nodular sclerosing Hodgkin lymphoma, amplification of the chromosomal region 9p24.1, which contains the genes PD-L1 (CD274), PDCD1LG2 (PD-L2)and JAK2, is directly correlated with increased expression of these proteins on Reed–Sternberg cells.
Overall, 105 of 108 (97%) biopsies from patients with newly diagnosed classical Hodgkin lymphoma have increased PD-L1 and PDCD1LG2 copy numbers. The prevalence and utility of PD-L1amplification as a response biomarker to PD-1/PD-L1 blockade is unknown in other tumors.
Response: Standard treatment for advanced urothelial cancer includes cisplatin-based chemotherapy which has been shown to improve survival. But more than half of patients are not expected tolerate it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative to cisplatin. Pembrolizumab is a PD-1 blocking antibody that reactivates the body's cancer-fighting T-cells (part of the immune system) to fight urothelial cancer.
The trial overall enrolled 374 patients who had not yet received any treatment for advanced urothelial cancer, but were considered ineligible for cisplatin chemotherapy.