November 9, 2020
Istari Oncology Presents Positive Data from Phase 1 Study
Istari Oncology Presents Positive Data from Phase 1 Study of PVSRIPO in Patients with Unresectable Treatment Refractory Melanoma at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting
- Data suggest that PVSRIPO, either alone or in combination with anti-PD-1, holds promise for patients with anti-PD-1 refractory melanoma
- Intratumoral PVSRIPO prompts systemic immune activation, which may explain responses in uninjected tumors seen in this study
- Data presented suggest PVSRIPO may help rekindle anti-tumor activity among immune checkpoint-failing patients
- Intratumoral PVSRIPO was well tolerated with no serious adverse events (SAEs) or dose- limiting toxicities (DLTs)
- These positive data clear the way for upcoming Phase 2 combination trial of PVSRIPO with or without anti-PD-1 therapy
DURHAM, NC, November 9, 2020 – Istari Oncology, Inc., a clinical-stage biotechnology company, today announced Phase 1 clinical data of its lead product candidate, PVSRIPO, for the treatment of patients with anti-PD-1 refractory melanoma at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting being held virtually from November 9-14, 2020.
PVSRIPO is a novel immunotherapy consisting of a non-neurovirulent rhinovirus:poliovirus chimera that activates innate and adaptive immunity to facilitate a targeted anti-tumor immune response. Among the 6 patients who received three PVSRIPO injections (maximum number administered, separated by 21 days) without any other concomitant therapy, the overall response rate was 67% (4/6), suggesting that PVSRIPO was able to initiate or rekindle responses in patients who have failed anti-PD-1 therapy. Responses in both injected and uninjected tumors (e.g. an abscopal response) were observed.
“There is a growing population of anti-PD1 refractory patients with unresectable melanoma who have no good treatment options available to them,” said Georgia Beasley, MD, Principal Investigator of the Phase 1 study at Duke University. “We are excited and encouraged by the preliminary results observed in our patients with advanced melanoma, refractory to anti-PD-1 and BRAF/MEK therapy. PVSRIPO was also very well tolerated in this advanced patient population, with no serious or dose limiting toxicities.”
“We are enthusiastic about these results, and their implications regarding the therapeutic potential of PVSRIPO,” said W. Garrett Nichols, MD, MS, Chief Medical Officer at Istari
Oncology. “PVSRIPO appears uniquely capable of engaging both innate and adaptive immune responses to generate antitumor immunity. As we move ahead into Phase 2 studies in patients with advanced unresectable melanoma who have failed anti-PD-1 therapy, we believe that the potential for PVSRIPO to generate an abscopal response in injected and non-injected tumors may vastly expand the addressable therapeutic population and improve patient prognosis. We look forward to further evaluating PVSRIPO in both this indication and other solid tumor types, as well as in our other ongoing trials in glioblastoma.”
The Phase 1 open-label trial (clinicaltrials.gov NCT03712358) enrolled 12 patients with unresectable and/or metastatic melanoma (American Joint Committee on Cancer stage IIIB, IIIC, or IV), who failed ≥1 anti-PD-1-based regimen; patients with BRAFᵛ⁶⁰⁰ mutations also failed ≥1 BRAF-targeted therapy. The primary objective of the Phase 1 study was to evaluate the safety and tolerability and explore the efficacy and immune activation of PVSRIPO in patients with advanced melanoma.
The data showed intratumoral PVSRIPO was well tolerated (all adverse events grade 1 or 2), with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs). There was no evidence of viral spread from the intratumoral inoculation site; pre-existing anti-poliovirus immunity and CD155 targeting are the likely mechanisms responsible for restricting viral spread and off- target/systemic immune related AEs.
Among the 12 treated patients, 4 (33%) met criteria for overall response rate (ORR) per immune-related response criteria, including 4/6 (67%) who received 3 injections. Pathologic complete response was observed in 2 of 4 (50%) patients with in-transit disease, showing evidence of abscopal response. Following the study’s completion, the majority of patients received additional immune checkpoint inhibitor (ICI)-based therapy and 6 out of 12 patients (50%) remained progression free at the data cutoff.
Collectively, these data suggest that PVSRIPO holds promise in anti-PD-1 refractory melanoma and further evaluation and in combination with anti-PD-1 therapy is warranted. As such, a protocol amendment exploring PVSRIPO treatment in more lesions per treatment cycle is ongoing, and the LUMINOS-102 Phase 2 study evaluating the safety and efficacy of PVSRIPO with and without anti-PD-1 therapy in the advanced anti-PD-1 refractory melanoma population is initiating; see NCT04577807 at clinicaltrials.gov for more information.
Details of Istari poster presentation:
Title: (#) A Phase I Trial of Intratumoral PVSRIPO in Patients with Unresectable Treatment Refractory Melanoma
Abstract Authors: Georgia M. Beasley, MD, MHs, Nellie E. Farrow, MD, Karenia Landa, MD, Maria Angelica Seilm, MD, Sin-Ho Jung, PhD, Darell D. Bigner, MD, PhD,
Andrea True Kelly, Ph, Smita Nair, Ph, Matthias Gromeier, MD, April Salama, MD
Presentation times: Thursday, Nov. 12 from 4:50–5:20 p.m. EST and Saturday, Nov. 14 from 1– 1:30 p.m. EST Location: Virtual Poster Hall
PVSRIPO is a virus based on the live attenuated Sabin type 1 polio vaccine that has been genetically modified for safety. Unlike other viral immunotherapies, PVSRIPO has a distinct target (the poliovirus receptor CD155), which is widely expressed in neoplastic cells of most solid tumors. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive antitumor immune responses via sublethal infection of antigen presenting cells in the tumor, which unleashes an inflammatory cascade resulting in sustained systemic antitumor immunity.
PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma.
There are estimated to be over 12,000 new and recurrent cases of advanced, unresectable melanoma diagnosed in the U.S. each year, and around 7,000 deaths. While immune checkpoint inhibitors have dramatically improved the outlook for advanced melanoma patients today, most patients treated with these immunotherapies are either primary non-responders or eventually develop immune-refractory progressive disease and require additional therapy.
About Istari Oncology
Istari Oncology, Inc., headquartered in Research Triangle Park, North Carolina, is a privately held clinical-stage biotechnology company focused on novel immune-oncology and immunotherapy platforms for the treatment of glioblastoma and a wide variety of tumors. The company was founded by Darell Bigner, MD, PhD and Matthias Gromeier, MD, of Duke University Medical Center in 2016. Istari licensed a broad range of patents and patent applications from Duke University and has access to additional intellectual property to continue clinical and commercial development of these technologies. The Company’s two platforms currently in clinical development are PVSRIPO and Antibody-Directed Immuno-Conjugates (ADC; eg, D2C7). For more information, please visit: www.istarioncology.com.
Istari Oncology Medical Affairs Contact:
Stern Investor Relations Christina Tartaglia
Media Contact: French/West/Vaughan Emily Brice