Phase 2 Study of Monotherapy with Pembrolizumab for Advanced Adrenocortical Carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a rare cancer with suboptimal response to chemotherapy. The role of immunotherapy in ACC management is evolving. Methods: An investigator-initiated, open-label, phase 2 clinical trial was performed to ascertain the activity and safety of monotherapy with pembrolizumab (a humanized monoclonal anti-programmed cell death protein 1 antibody) in patients with advanced ACC. This study was part of a basket clinical trial (ClinicalTrials.gov ID: NCT02721732). Study participants were enrolled from August 15, 2016, until December 7, 2020. Pembrolizumab (200 mg) was administered intravenously every 3 weeks. All other lines of therapy, including mitotane, were stopped before pembrolizumab initiation. The primary endpoint was the nonprogression rate (being alive without progression) at 27 weeks, which was objectively assessed by an independent radiology team based on the immune-related response evaluation criteria in solid tumors. Secondary endpoints consisted of adverse events assessed using the Common Terminology Criteria for Adverse Events (version 4.03). Results: We enrolled 23 patients with ACC (13 women [57%]) with a median age of 54 years (range, 31-78 years). Four cases were cortisol producing (17%). The median follow-up calculated by reverse Kaplan-Meier was 66.9 months. Among the 23 patients, three were not evaluable for response; two patients stopped treatment because of toxicity and did not undergo restaging scans, and one patient withdrew consent for follow-up owing to international relocation. Among 20 patients with evaluable response, six (30%) were alive without progression at 27 weeks. We saw no complete responses but did see partial responses in four patients (20%) with a mean duration of response of 17.6 months (95% CI, 9.6-25.6). The median progression-free survival time was 4.0 months (95% CI, 2.0-6.2 months), and the median overall survival time was 15.5 months (95% CI, 6.2-22.8 months). The clinical benefit rate was 30% (complete response, partial response, and stable disease at 27 weeks (after 3 radiographic evaluations). Three treatment-related adverse events were grade 3 or higher. Microsatellite instability statuses were not available. No treatment-related deaths occurred. Conclusions: Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile.