Pembrolizumab in recurrent or metastatic medullary thyroid cancer

It has been hypothesized that sequencing antigen-directed immunotherapy with immune checkpoint inhibitors could prime a tumor for immune response to immune checkpoint inhibitors.

This study (NCT03072160) was designed to evaluate two cohorts of patients with medullary thyroid cancer, a cancer that is not known to have therapeutic responses to immune checkpoint inhibitors. One cohort included patients with previous immunotherapy (GI-6207, an experimental therapeutic cancer targeting carcinoembryonic antigen), and a second cohort included patients with no previous history of GI-6207. All patients were treated with standard of care dosing of pembrolizumab, 200 mg every 3 weeks for up to 2 years. Patients were followed with imaging every 3 months. Peripheral blood mononuclear cells (PBMCs) were evaluated at 3 months for immune responses.

17 patients were enrolled on this study. Among the 13 patients with previous immunotherapy (GI-6207), the median age was 52.4 years. Among the 4 patients with no previous immunotherapy the median age was 58.8 years. No patients in either cohort had evidence of therapeutic response. No patients had confirmed 50% declines in either serum carcinoembryonic antigen or calcitonin. No radiographic responses were observed. There was no evidence of immune impact of pembrolizumab in analysis of PBMCs. Given the lack of responses in the previous immunotherapy cohort, the study was closed early. No new safety signals were observed.

This study did not support the hypothesis that sequencing immunotherapy with an immune checkpoint inhibitor could enhance the clinical activity of the immune checkpoint, which has not demonstrated independent activity in that disease previously.