A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies.

BACKGROUND: LHC165 is a Toll-like receptor (TLR)-7 agonist that generates an effective tumor antigen-specific T-cell adaptive immune response as well as durable antitumor responses. We aimed to evaluate the safety, tolerability, efficacy, dose-limiting toxicities, and pharmacokinetics (PK) of LHC165 single agent (SA) ± spartalizumab [PDR001; anti-programmed cell death protein 1 (PD-1)] in adult patients with advanced solid tumors. MATERIALS AND METHODS: In this phase I/Ib, open-label, dose-escalation/expansion study, patients received LHC165 SA 100-600 µg biweekly through intratumoral (IT) injection and LHC165 600 µg biweekly + spartalizumab 400 mg Q4W through intravenous (IV) infusion. RESULTS: Forty-five patients were enrolled: 21 patients received LHC165 SA, and 24 patients received LHC165 + spartalizumab. The median duration of exposure was 8 weeks (range 2-129 weeks). No maximum tolerated dose was reached. Recommended dose expansion was established as LHC165 600 µg biweekly as SA and in combination with spartalizumab 400 mg Q4W. The most common drug-related adverse events (AEs) were pyrexia (22.2%), pruritus (13.3%), chills (11.1%), and asthenia (4.4%). The only serious AE (SAE) suspected to be related to the study drug was grade 3 pancreatitis (n = 1). Across all tumor types, overall response rate and disease control were 6.7% and 17.8%, respectively. Overall median progression-free survival (PFS) and immune-related PFS was 1.7 months. LHC165 serum PK demonstrated an initial rapid release followed by a slower release due to continued release of LHC165 from the injection site. CONCLUSIONS: LHC165 demonstrated acceptable safety and tolerability both as SA and in combination with spartalizumab, and evidence of limited antitumor activity was seen in adult patients with relapsed/refractory or metastatic solid tumors.

A study on the reproducibility of a stable, lyophilized reagent for the Chagas' disease hemagglutination test: proposals for quality control analysis.

Para se efetuar rigoroso controle de partidas sucessivas de reagentes liofilizados, usados na reacao de hemaglutinacao passiva, sao aqui propostos processos estatisticos simples. Para se avaliar qualitativamente os niveis de sensibilidade e de especificidade do reagente foi empregada a analise sequencial truncada.Os criterios adotados na avaliacao foram definidos com base em estudos comparativos efetuados com o teste de hemaglutinacao passiva em relacao as reacoes de imunofluorescencia, fixacao do complemento e floculacao de 3.264 soros de individuos, infectados ou nao pelo T. cruzi. Onze partidas de reagente de hemaglutinacao, produzidas durante um periodo de 3 anos, foram submetidas a esta analise de qualidade. O processo aqui proposto mostrou-se satisfatorio para selecionar reagentes que forneceram resultados reprodutiveis. Esta observacao foi confirmada quando se procedeu a analise de variancia dos resultados obtidos com 7 partidas de reagentes, aprovados pela analise de qualidade, contra 20 soros de pacientes chagasicos titulados em duplicata