lerapolturev (PVS-RIPO)

P1/2, N=4, Terminated, Istari Oncology, Inc. | N=15 --> 4 | Trial completion date: May 2025 --> Jun 2024 | Recruiting --> Terminated | Trial primary completion date: May 2025 --> Apr 2024; business decision

P2, N=56, Active, not recruiting, Istari Oncology, Inc. | Trial primary completion date: Jun 2024 --> Oct 2024

P2, N=25, Completed, Istari Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Mar 2024 --> Jun 2024

P1, N=12, Terminated, Istari Oncology, Inc. | Completed --> Terminated; Study closed to enrollment due to business decision prior to enrolling Cohort 4

P2, N=92, Not yet recruiting, Darell Bigner | Initiation date: Apr 2024 --> Jul 2024

P1, N=8, Completed, Istari Oncology, Inc. | Active, not recruiting --> Completed | Phase classification: P1b --> P1 | N=12 --> 8

P2, N=56, Active, not recruiting, Istari Oncology, Inc. | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Jun 2024

P2, N=92, Not yet recruiting, Darell Bigner | Initiation date: Dec 2023 --> Apr 2024

P1, N=5, Completed, Istari Oncology, Inc. | Recruiting --> Completed

P2, N=92, Not yet recruiting, Darell Bigner

Convection enhanced delivery of lerapolturev is safe enough in the treatment of recurrent paediatric high-grade glioma to proceed to the next phase of trial.

P2, N=56, Recruiting, Istari Oncology, Inc. | Trial completion date: May 2023 --> Oct 2023 | Trial primary completion date: Apr 2023 --> Oct 2023

An inflamed pretreatment tumor microenvironment, possibly induced by prior anti-PD-1 therapy and a proficient peripheral blood pretreatment innate immune response (antiviral/interferon signaling) to lerapolturev was associated with long term PFS after intratumoral lerapolturev in a small cohort of patients. These findings imply a link between intratumoral T cell inflammation and peripheral immune function.

The capacity of relevant innate stimulating immunotherapies to induce CXCR3 ligands in human glioma tissue was assessed using an ex vivo glioma slice culture assay, and the contribution of CXCR3 signaling to polio virotherapy (PVSRIPO) and STING agonist therapy was tested in murine models... This work indicates that CXCR3 signaling, a key contributor to cancer immune surveillance, is disrupted in human gliomas relative to other solid tumor types. Intratumor virotherapy and STING agonists hold potential to rectify diminished CXCR3 ligand expression in gliomas.

P1, N=12, Completed, Istari Oncology, Inc. | Active, not recruiting --> Completed | N=18 --> 12

P2, N=56, Recruiting, Istari Oncology, Inc. | Active, not recruiting --> Recruiting

P1/2; Recruiting --> Active, not recruiting

P2, N=56, Active, not recruiting, Istari Oncology, Inc. | Recruiting --> Active, not recruiting

P1, N=18, Active, not recruiting, Istari Oncology, Inc. | Trial completion date: Dec 2021 --> Apr 2022 | Trial primary completion date: Dec 2021 --> Mar 2022

Immunotherapy with polio:rhinovirus recombinant (PVSRIPO) has shown evidence of efficacy in a phase I clinical trial for recurrent GBM, resulting in durable radiographic responses and 21% long-term survival at 36 months...Thus, buttressing type-I IFN directed antitumor CD8+T cell immunity, e.g. with blockade of the PD1:PD-L1 immune checkpoint, might contribute to tumor remission. Indeed, combination therapy with αPD-L1 antibody in the CT2A model showed longer median survival and higher long-term remission rate compared to monotherapy alone; CD8 T cell depletion can completely abrogate this efficacy with this therapy combination, confirming the role of anti-tumor immunity in this approach.

Conclusions Childhood vaccine-specific CD4+ T cells hold cancer immunotherapy potential. In the context of PVSRIPO therapy, antitumor and inflammatory effects of polio vaccine-specific CD4+ T cell recall supersedes inhibitory effects of attenuated intratumor viral replication, and represents a novel mechanism of action.

P1, N=6, Recruiting, Istari Oncology, Inc. | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Jul 2021 --> Jul 2022

P1b, N=12, Active, not recruiting, Istari Oncology, Inc. | Trial primary completion date: Jun 2021 --> Dec 2021

P1b, N=12, Active, not recruiting, Istari Oncology, Inc. | Recruiting --> Active, not recruiting

Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients.

P1b, N=12, Recruiting, Istari Oncology, Inc. | Trial primary completion date: Mar 2021 --> Jun 2021

This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy...As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies.

P1, N=18, Active, not recruiting, Istari Oncology, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021

P1b, N=12, Recruiting, Istari Oncology, Inc. | Trial completion date: Jul 2021 --> Mar 2022 | Trial primary completion date: Jul 2020 --> Mar 2021

P2, N=56, Recruiting, Istari Oncology, Inc. | Not yet recruiting --> Recruiting

P1, N=18, Recruiting, Istari Oncology, Inc. | N=12 --> 18

P2, N=50, Not yet recruiting, Istari Oncology, Inc.

P1, N=12, Active, not recruiting, Istari Oncology, Inc. | Recruiting --> Active, not recruiting

P1, N=0, Withdrawn, Darell Bigner | N=30 --> 0 | Not yet recruiting --> Withdrawn

P1, N=30, Not yet recruiting, Darell D. Bigner, MD, PhD | Initiation date: Dec 2019 --> Jun 2020