Durable response of anaplastic thyroid carcinoma to FS118, a bispecific LAG-3/PD-L1 antibody, after checkpoint inhibitor progression: a case report

Anaplastic thyroid cancer represents a rare, highly aggressive form of thyroid cancer with a poor prognosis and an overall survival ranging from 5 to 12 months. Unfortunately, treatment options remain limited, even for patients with a targetable driver mutation. Here, we present a case of a patient with a BRAF V600E-mutated, PD-L1 positive (tumor proportion score of 95%) anaplastic thyroid cancer refractory to standard therapies, including debulking surgery, followed by chemoradiation, who had further progressed on PD-1 monotherapy, and was unable to tolerate BRAF/MEK inhibition. Ongoing treatment with FS118, a bispecific LAG-3/PD-L1 antagonist, has afforded 3 years of disease control, including a late confirmed partial response, with excellent tolerability. Given this response, further investigation is required to delineate the mechanism by which dual PD-L1/LAG-3 blockade by FS118 overcomes initial PD-1 pathway resistance, and therefore, identify which patients are most likely to benefit. Simultaneously, expanded use should be considered for those with refractory disease, especially if PD-L1 positive. Insights Dual PD-L1/LAG-3 blockade may be an effective treatment strategy for refractory metastatic tumors, including anaplastic thyroid cancer.

Automated summary

This article presents a case of a patient with BRAF V600E-mutated, PD-L1 positive anaplastic thyroid cancer refractory to standard therapies, but achieving 3 years of disease control and partial response through treatment with FS118. Further investigation is needed to understand the mechanism of dual PD-L1/LAG-3 blockade by FS118 in overcoming initial PD-1 pathway resistance.