@article {Nainge000530, author = {Aung Naing and Justin F Gainor and Hans Gelderblom and Patrick M Forde and Marcus O Butler and Chia-Chi Lin and Sunil Sharma and Maria Ochoa de Olza and Andrea Varga and Matthew Taylor and Jan H M Schellens and Hongqian Wu and Haiying Sun and Antonio P Silva and Jason Faris and Jennifer Mataraza and Scott Cameron and Todd M Bauer}, title = {A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti{\textendash}PD-1 antibody, in patients with advanced solid tumors}, volume = {8}, number = {1}, elocation-id = {e000530}, year = {2020}, doi = {10.1136/jitc-2020-000530}, publisher = {BMJ Specialist Journals}, abstract = {Background Spartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.Methods In the phase 1 part of the study, 58 patients received spartalizumab, intravenously, at doses of 1, 3, or 10 mg/kg, administered every 2 weeks (Q2W), or 3 or 5 mg/kg every 4 weeks (Q4W).Results Patients had a wide range of tumor types, most commonly sarcoma (28\%) and metastatic renal cell carcinoma (10\%); other tumor types were reported in <=3 patients each. Most patients (93\%) had received prior antineoplastic therapy (median three prior lines) and two-thirds of the population had tumor biopsies negative for PD-L1 expression at baseline. The maximum tolerated dose was not reached. The recommended phase 2 doses were selected as 400 mg Q4W or 300 mg Q3W. No dose-limiting toxicities were observed, and adverse events included those typical of other PD-1 antibodies. The most common treatment-related adverse events of any grade were fatigue (22\%), diarrhea (17\%), pruritus (14\%), hypothyroidism (10\%), and nausea (10\%). Partial responses occurred in two patients (response rate 3.4\%); one with atypical carcinoid tumor of the lung and one with anal cancer. Paired tumor biopsies from patients taken at baseline and on treatment suggested an on-treatment increase in CD8+ lymphocyte infiltration in patients with clinical benefit.Conclusions Spartalizumab was well tolerated at all doses tested in patients with previously treated advanced solid tumors. On-treatment immune activation was seen in tumor biopsies; however, limited clinical activity was reported in this heavily pretreated, heterogeneous population. The phase 2 part of this study is ongoing in select tumor types.Trial registration number NCT02404441.}, URL = {https://jitc.bmj.com/content/8/1/e000530}, eprint = {https://jitc.bmj.com/content/8/1/e000530.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }