Phase I clinical study of @entity72328 ( XXXX -001), a replication-competent picornavirus, in advanced solid @entity5 with @entity154 .

@entity1 @entity154 @entity72328 @entity6355 @entity137 @entity4153 @entity5 @entity151
PURPOSE: @entity72328 ( @entity6355 -001) is a novel naturally occurring replication-competent picornavirus with potent and selective tropism for neuroendocrine @entity5 cell types, including @entity151 . We conducted a first-in- @entity1 , first-in-class phase I clinical trial of this agent in @entity1 with @entity5 with @entity154 , including @entity151 . EXPERIMENTAL DESIGN: Clinical evaluation of single intravenous doses in @entity1 with @entity5 with @entity154 was performed across five log-increments from 10(7) to 10(11) vp/kg. @entity137 , viral titers and clearance, neutralizing antibody development, and @entity5 response were assessed. RESULTS: A total of 30 @entity1 were treated with @entity6355 -001, including six with @entity4153 at the lowest dose of 10(7) vp/kg. @entity6355 -001 was well tolerated, with no dose-limiting @entity137 observed in any dose cohort. Viral clearance was documented in all subjects and correlated temporally with development of antiviral antibodies. Evidence of in vivo intratumoral viral replication was observed among @entity1 with @entity4153 , with peak viral titers estimated to be >10(3)-fold higher than the administered dose. One @entity1 with previously progressive @entity151 remained progression-free for 10 months after @entity6355 -001 administration, and is alive over 3 years after treatment. CONCLUSIONS: Intravenous @entity6355 -001 administration in @entity1 is well tolerated at doses up to 10(11) vp/kg, with predictable viral clearance kinetics, intratumoral viral replication, and evidence of antitumor activity in @entity1 with @entity151 . Phase II clinical evaluation in @entity151 is warranted, and has been initiated.
