Background: The anti–PD-1 antibody pembro is approved in the US for treating advanced MEL that progressed following IPI and, if BRAF^V600 mutant, a BRAF inhibitor. Immune-related AEs (irAEs) are of interest for immunotherapies such as pembro. Among the first 411 MEL pts treated with pembro in the phase 1 KEYNOTE-001 study (NCT01295827), 18% experienced irAEs (4% gr 3/4). We describe the incidence and treatment of thyroid disorders, the most common irAEs observed in KEYNOTE-001. Methods: AEs were monitored throughout treatment and for 30 d thereafter (serious AEs and potential irAEs for up to 90 d). AEs were graded per CTCAE v4.0. Thyroid disorders included hypothyroidism, hyperthyroidism, thyroiditis, and related terms. TSH and free T4 (FT4) levels were measured at baseline and once per treatment cycle. Results: Thyroid disorders occurred in 39 (9.5%) pts: hypothyroidism in 33 (8.0%), hyperthyroidism in 6 (1.5%), and thyroiditis in 3 (0.7%); 2 pts experienced both hypo- and hyperthyroidism, and 1 pt experienced hypothyroidism and thyroiditis. 2 events were of gr 3 severity: 1 hypo- and 1 hyperthyroidism. Hypothyroidism was managed with long-term hormone replacement therapy, with no permanent discontinuation required; only 4 pts required temporary pembro interruption. 2 pts with hyperthyroidism required corticosteroids, and 2 permanently discontinued pembro. Hyperthyroidism resolved in 83% of pts. Thyroiditis resolved in 67% of pts; no cases required treatment interruption, discontinuation, or corticosteroid use. Median time to onset and duration are shown in the Table. 111 (33.9%) pts had ≥1 abnormal postbaseline TSH or FT4 value, with subclinical hypo- and hyperthyroidism most common (20.5% and 19.3%, respectively). Conclusions: Thyroid disorders are the most frequent irAEs associated with pembro. Most events are of gr 1 or 2 severity and can be managed with supportive care and temporary treatment interruption. These findings support regular assessment of thyroid function in pembro recipients. Clinical trial information: NCT01295827