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Ref Type Journal Article
PMID (32179633)
Authors Naing A, Gainor JF, Gelderblom H, Forde PM, Butler MO, Lin CC, Sharma S, Ochoa de Olza M, Varga A, Taylor M, Schellens JHM, Wu H, Sun H, Silva AP, Faris J, Mataraza J, Cameron S, Bauer TM
Title A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors.
URL
Abstract Text 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.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).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.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.NCT02404441.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Spartalizumab Spartalizumab 2 10
Drug Name Trade Name Synonyms Drug Classes Drug Description
Spartalizumab PDR001|PDR-001 Immune Checkpoint Inhibitor 147 PD-L1/PD-1 antibody 117 Spartalizumab (PDR001) is a monoclonal antibody that targets PD-1 (PDCD1) and inhibits binding of the PD-L1 (CD274) ligand, potentially resulting in enhanced anti-tumor immune response (PMID: 32364844, PMID: 32179633).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 positive anal canal cancer predicted - sensitive Spartalizumab Case Reports/Case Series Actionable In a Phase I trial, Spartalizumab (PDR001) treatment in a patient with CD274 (PD-L1)-positive anal cancer resulted in a partial response lasting 1.8 months, with a combined 31% reduction of target lesion size (PMID: 32179633; NCT02404441). 32179633