PT  - JOURNAL ARTICLE
AU  - Aung Naing
AU  - Justin F Gainor
AU  - Hans Gelderblom
AU  - Patrick M Forde
AU  - Marcus O Butler
AU  - Chia-Chi Lin
AU  - Sunil Sharma
AU  - Maria Ochoa de Olza
AU  - Andrea Varga
AU  - Matthew Taylor
AU  - Jan H M Schellens
AU  - Hongqian Wu
AU  - Haiying Sun
AU  - Antonio P Silva
AU  - Jason Faris
AU  - Jennifer Mataraza
AU  - Scott Cameron
AU  - Todd M Bauer
TI  - A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti–PD-1 antibody, in patients with advanced solid tumors
AID  - 10.1136/jitc-2020-000530
DP  - 2020 Mar 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e000530
VI  - 8
IP  - 1
4099  - http://jitc.bmj.com/content/8/1/e000530.short
4100  - http://jitc.bmj.com/content/8/1/e000530.full
SO  - J Immunother Cancer2020 Mar 01; 8
AB  - 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.