Phase II Trial of Pembrolizumab in Patients with Platinum Refractory Germ Cell Tumors: A Hoosier Cancer Research Network Study GU14-206

Background

Despite remarkable results with salvage standard-dose or high-dose chemotherapy about 15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT.

Patients and Methods

Single arm phase 2 trial investigating pembrolizumab 200mg IV Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at-least 1 salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary endpoint was overall response rate (ORR) using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized.

Results

12 male patients were enrolled. Median age 38. All patients had non-seminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range,1-32,760) and hCG 4 (range,0.6-37,096). 6 patients had late relapse (>2years). Median number of previous chemotherapy regimens was 3. 6 patients received prior high-dose chemotherapy. 2 patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range,1-8). There were 6 grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. 2 patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining.

Conclusion

This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT.Clinical trial information:NCT02499952.