1619O High clinical benefit rates of single agent pembrolizumab in selected rare sarcoma histotypes: First results of the AcSé Pembrolizumab study

Abstract

AcSé Pembrolizumab is a phase II, non-randomized parallel arm, open-label, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with rare cancers (NCT03012620). Here we report the results of pembrolizumab in the rare sarcoma cohort. Selected histotypes were all rare sarcomas (incidence <0.2/100,000/year). Main inclusion criteria were age>18, PS≤1, and advanced disease resistant to standard treatment. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to RECIST v1.1. Secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), and safety. Five groups of patients were distinguished, namely chordoma, alveolar soft-part sarcoma (ASPS), desmoplastic small round cell tumor (DSRCT), smarca4-malignant rhabdoid tumor (SMBT) and the others. 80 patients with rare sarcomas, including 24 with chordoma, 13 ASPS, 6 DSCRCT, 6 SMBT and 31 with other histotypes, were included from July 2017 to February 2020. The median number of cycles was 5 (range, 1 to 33) with 54 (67.5%) patients who discontinued the trial after a median of 4 cycles. Twenty-eight patients died after a median of 3 cycles (linked to cancer 27, other 1). Best response was PR in 13 patients (16.25%, 95%CI: 8.9 to 26.2%), and SD in 29 (36.25%). The occurrence of best response depended on the histotype, with 2 (8%) responses in chordoma, 5 (39%) in ASPS, 1 (17%) in DSCRCT, 3 (50%) in SMBT, and 2 (6%) in other histotypes (p=0.010). At data cut off, the 1-year PFS rates of the five histotype groups were 35%, 58%, 0, 62.5%, and 8%, with median times of 5.7 months, 14 months, 5, not reached, and 2.7 months respectively (p= 0.00016), while 1-year OS rates were 72%, 90%, 50%, 83% and 40% (p= 0.02). Median survival were only reached for chordoma (20 months), DSRCT (7.4 months), and other histotype group (5.4 months). Pembrolizumab shows high levels of prolonged activity in selected subtypes of rare sarcomas.