Accelovance (United States)

169 Background: GT0918 is a new chemical entity of androgen receptor (AR) blocker. A phase I/II study was conducted to identify dose-limiting toxicities (DLTs) and to assess safety, tolerability, and PK of GT0918 in pts with mCRPC who have progressed on standard of care (SoC) and experimental therapies in the United States. Methods: Patients (pts) with histologically confirmed mCRPC who had progressed after both hormonal therapy (abiraterone or/and enzalutamide) and chemotherapy (e.g., docetaxel) were eligible. GT0918 was administered once daily orally for 28 consecutive days, followed by a 7-day off-treatment period for PK analysis. The first 28-days on treatment (cycle 1) was defined as DLT period. Pts continued on receiving GT0918 thereafter until they experienced one of following events of intolerable toxicities, disease progression or withdrew consent. Results: 35 pts were enrolled to GT0918-US-1001 trial with 6 dose escalations of study drug defined in protocol: 50 mg (n = 3), 100 mg (n = 6), 200 mg (n = 6), 300 mg (n = 7), 400 mg (n = 7) and 500 mg (n = 6). All pts progressed on multiple lines of therapies including but limited to bicalutamide, abiraterone, enzalutamide, docetaxel, cabazitaxel, radium 223, sipuleucel T and pembrolizumab. No DLT was observed and MTD has not been reached. GT0918 related adverse events (AEs) were less than 10% and grade 1 or 2 as per CTCAE v4.03, including fatigue, nausea, dizziness, loss of appetite, back pain, hot flush, hypercholesterolemia, anemia, constipation, etc. Two events of grade 3 fatigue and one event of grade 4 elevated creatine kinase (CK) were reported. Stable disease by imaging scans at 24 weeks by dose group were; 1/50 mg, 1/100mg, and 4/400mg. Three pts on 500mg finished 3 cycles and continue on the treatment (as 10/15/18). PSA decreases were also seen among pts at 500mg dose level for 4 cycles. Conclusions: GT0918 administrated orally once a day is well tolerated and resulted in SD in late-stage pts. No DLT has occurred to date (at 500 mg) and dose escalation is planned to 600 mg or higher. Extended/Ph II trial will further evaluate safety and efficacy of GT0918 in mCRPC pts. Clinical trial information: NCT02826772.

Background. Highly pathogenic avian influenza H5N1 viruses remain a threat to human health, with potential to become pandemic agents.Methods. This phase III, placebo-controlled, observer-blinded study evaluated the immunogenicity, cross-reactivity, safety, and lot consistency of 2 doses of oil-in-water (AS03A) adjuvanted H5N1 A/Indonesia/05/2005 (3.75 μg hemagglutinin antigen) prepandemic candidate vaccine in 4561 adults aged 18–91 years.Results. Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for pandemic vaccines in all age strata 21 days after the second dose. At 6 months after the administration of the primary dose, serum antibody seroconversion rates continued to fulfill licensure criteria. Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004. Consistency was demonstrated for 3 consecutive H5N1 vaccine lots. Temporary injection-site pain was more frequent with H5N1 vaccine than placebo (89.3% and 70.7% in the 18–64 and ≥65 years strata vs 22.2% and 14.4% in the placebo groups). Unsolicited adverse event frequency, including medically attended and serious events, was similar between groups through day 364.Conclusions. In adults and elderly adults, AS03A-adjuvanted H5N1 candidate vaccine was highly immunogenic for A/Indonesia/05/2005, with cross-reactivity against A/Vietnam/1194/2004. Temporary injection site reactions were more frequent with H5N1 vaccine than placebo, although the H5N1 vaccine was well tolerated overall.Clinical Trials Registration. NCT00616928.