Pembrolizumab in patients with recurrent thymic carcinoma: Results of a phase II study.

Abstract

8573 Background: There are few treatment options for thymic carcinoma after chemotherapy. We completed a single institution phase II study of pembrolizumab (P) in patients with recurrent thymic carcinomas. Methods: Main eligibility criteria included: progression after ≥ 1 chemotherapy line, ECOG PS 0-2, no history of autoimmune disease, and adequate organ function. P was given at 200mg IV every 3 weeks. The primary objective of the study was response rate (RR) by RECIST v1.1 criteria; secondary objectives were PFS and OS, and safety. Results: From 3/2015 to 12/2016 we accrued 41 patients. Of 40 eligible patients, 29 were male, 19 Caucasians, median age was 57 years (range 25-80), 14 had squamous carcinoma histology, and 19 ECOG PS 0. Median number of cycles delivered was 6 (range 1-31). The most common side effects were mild fatigue (10), diarrhea (4) and rhinorrhea (4). Six patients developed multiple grade 3-4 immune-relates AEs (irAEs): myocarditis/myositis (1), myositis/myocarditis/hepatitis/myasthenia gravis (1), myositis/hepatitis (1), bullous pemphigoid (1), hepatitis (1), hepatitis/pancreatitis/diabetes mellitus type 1 (1). There were no treatment related deaths. The 2 patients who developed myocarditis required a pacemaker. Three patients interrupted treatment because of irAEs (all responders) and 3 because of progression around the time of the irAE. irAEs were more frequent in females (4/6; p = .026). Five patients developed hypothyroidism and 1 hyperthyroidism. RR assessed in all 40 eligible patients was 22.5%: 1 complete response, 8 partial responses (plus 1 unconfirmed), 20 stable disease and with 11 progressions. Two partial responses show minimal residual disease with no PET uptake. Two responders have progressed and 5 responses are beyond 12 months duration. Of 29 cases tested for PD-L1 staining (Dako 22C3), high PD-L1 (≥50% tumor cells positive) was seen in 8 (28%); 6/9 responders had high PD-L1 expression. Targeted NGS in 15 cases did not show correlation between mutational burden and response. Conclusions: P has activity in patients with thymic carcinoma. irAEs are more frequent than in other tumors. Further analysis of NGS, Nanostring and PD-L1 expression and updated survival will be presented. Clinical trial information: NCT02364076.