Search

ObjectiveTo evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. MethodsThis open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. ResultsAt November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. ConclusionSubcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors. [ABSTRACT FROM AUTHOR]

Abstract With the expansive use of immune checkpoint inhibitors, the frequency of immune‐related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti‐programmed death‐ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81‐year‐old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab‐induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors.

Background: In the PACIFIC study, progression-free survival (PFS) and overall survival (OS) of patients with unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC) were prolonged by durvalumab as maintenance therapy after radical concurrent chemoradiotherapy using platinum-based antitumor agents. However, no data were obtained to reveal the efficacy of durvalumab after radiation monotherapy in patients unsuitable for chemoradiotherapy. Here, we describe an ongoing single-arm, prospective, open-label, multicenter phase II trial of durvalumab in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study). Methods: Durvalumab at 10 mg/kg body weight is administered every 2 weeks after radiation therapy until individual patients meet the discontinuation criteria. The treatment duration is up to 12 months. The primary endpoint is the 1-year PFS rate. Secondary endpoints are response rate, PFS, OS, and safety. Durvalumab treatment after radiation monotherapy is expected to prolong 1-year PFS rate and have acceptable adverse events. Discussion: We are conducting an intervention study to investigate the safety and efficacy of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy. [ABSTRACT FROM AUTHOR]

With the expansive use of immune checkpoint inhibitors, the frequency of immune‐related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti‐programmed death‐ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81‐year‐old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab‐induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]