A phase 2 study of GI-6207 in patients with recurrent medullary thyroid cancer.

BACKGROUND

Medullary thyroid cancer (MTC) accounts for approximately 4% of thyroid carcinomas. Patients with unresectable, metastatic disease are candidates for approved agent-targeted therapies such as vandetanib, cabozantinib, or selpercatinib, but toxicity is often an issue. Preclinical data supported the potential use of immunotherapy targeting carcinoembryonic antigen (CEA) in this indolent disease.

METHODS

Patients with advanced/recurrent MTC were randomly assigned in a 1:1 ratio to receive a Saccharomyces cerevisiae (yeast)-based immunotherapy (GI-6207) targeting CEA starting at the time of enrollment or 6 months after surveillance. The primary endpoint was to compare the calcitonin growth rate in the GI-6207 arm at 6 months with patients in the surveillance arm at 6 months.

RESULTS

Between March 2013 and May 2018, 34 patients were randomly assigned to receive the yeast-CEA vaccine (GI-6207) starting at the time of enrollment or 6 months after surveillance. The mean age was 51 years, and 82% of patients were diagnosed with sporadic MTC. There was no significant change in the calcitonin growth rates at 6 months when the immunotherapy group was compared with the surveillance group (-2.490042 vs -2.526385; P = .3760). Treatment with GI-6207 was associated with increased peripheral CEA-specific CD4 and/or CD8 T cells, with 15/26 (58%) patients displaying increases after 3 months of treatment. One patient had a significant inflammatory event 17 months after the last vaccine at a known lymph node, perhaps related to a delayed immune response. There were no grade 3 or 4 adverse events. Grade 1 injection site reactions were most common.

CONCLUSION

The immunotherapy was well tolerated but did not have an impact on tumor growth rate at 6 months as measured by calcitonin kinetics.

CLINICAL TRIAL IDENTIFICATION: NCT01856920.