TY - JOUR T1 - Phase 2 study of pembrolizumab in patients with advanced rare cancers JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2019-000347 VL - 8 IS - 1 SP - e000347 AU - Aung Naing AU - Funda Meric-Bernstam AU - Bettzy Stephen AU - Daniel D Karp AU - Joud Hajjar AU - Jordi Rodon Ahnert AU - Sarina A Piha-Paul AU - Rivka R Colen AU - Camilo Jimenez AU - Kanwal P Raghav AU - Renata Ferrarotto AU - Shi-Ming Tu AU - Matthew Campbell AU - Linghua Wang AU - Sarjeel H Sabir AU - Coya Tapia AU - Chantale Bernatchez AU - Michael Frumovitz AU - Nizar Tannir AU - Vinod Ravi AU - Saria Khan AU - Jeane M Painter AU - Abulrahman Abonofal AU - Jing Gong AU - Anas Alshawa AU - Lacey M McQuinn AU - Mingxuan Xu AU - Sara Ahmed AU - Vivek Subbiah AU - David S Hong AU - Shubham Pant AU - Timothy A Yap AU - Apostolia M Tsimberidou AU - Ecaterina E Ileana Dumbrava AU - Filip Janku AU - Siqing Fu AU - Richard M Simon AU - Kenneth R Hess AU - Gauri R Varadhachary AU - Mouhammed Amir Habra Y1 - 2020/03/01 UR - http://jitc.bmj.com/content/8/1/e000347.abstract N2 - Background Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.Methods In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).Results A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma–pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.Conclusions The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma–pheochromocytoma supports further evaluation of pembrolizumab in this patient population.Trial registration number NCT02721732 ER -