Assessments
bleeding, neutropenia, toxicityMissing, toxicity, toxicities, Cancer
ADVERSE EVENT, BLEEDING, NEUTROPENIA, EVENT, HEMODYNAMIC INSTABILITY, CANCER
Patients were continuously monitored throughout the study for safety as outlined in the schedule of assessments in the study Protocol. AEs and serious AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events, version 4.03, and their relationship to treatment administered was assessed. For the dose-escalation phase, the dose-limiting toxicity (DLT) window of observation was the first 21 days after initial pembrolizumab infusion. The occurrence of any of the following toxicities is considered a DLT, if judged by the Investigator to be possibly, probably or definitely related to administration of DNX-2401 and pembrolizumab (and not to the administration procedure):Grade 4 nonhematologic toxicity (not laboratory)Grade 4 hematologic toxicity lasting ≥7 daysGrade 3 nonhematologic toxicity (not laboratory) lasting >3 days despite optimal supportive careAny Grade 3 or Grade 4 nonhematologic laboratory value if:Medical intervention is required to treat the subject, orThe abnormality leads to hospitalization, orThe abnormality persists for >1 weekFebrile neutropenia Grade 3 or Grade 4:Grade 3 is defined as ANC <1,000 mmGrade 4 is defined as ANC <1,000 mmThrombocytopenia <25,000 mmA bleeding event that does not result in hemodynamic instability but requires an elective platelet transfusion, orA life-threatening bleeding event which results in urgent intervention and admission to an Intensive Care Unit.Prolonged delay (>2 weeks) in initiating cycle 2 due to treatment-related toxicityMissing >10% of pembrolizumab doses as a result of AE(s) during the first cycleGrade 5 toxicityTreatment response was determined by serial protocolized contrast-enhanced MRI every 4 weeks for 28 weeks, and afterward at an interval of every 8 weeks for the remainder of the treatment period. Patients who completed the treatment phase entered the long-term response and survival follow-up phase of the study for the rest of life, with MRI every 16 weeks. Objective responses were evaluated by the RANO criteria