Groundbreaking Pivotal Study Conducted at the National Cancer Institute for PRGN-2012 in Patients with Recurrent Respiratory Papillomatosis (RRP), in Which More Than Half of Patients Achieved Complete Response.
June 3, 2024
RRP is a rare, devastating HPV-mediated chronic disease that causes wart-like (benign) growths in the airways. These growths can be removed by surgery but typically grow back. In 2023, the FDA granted the first-in-class investigational PRGN-2012 (a gorilla adenovirus–based gene therapy from Precigen Inc.) Breakthrough Therapy Designation and Orphan Drug Designation for the treatment of RRP. PRGN-2012 is being developed via a Cooperative Research and Development Agreement between the NCI and Precigen. The first-in-human, phase 1/2 pivotal study (NCT04724980) of PRGN-2012 in adult patients with RRP, conducted at the NCI and led by Scott M. Norberg, D.O., Associate Research Physician in the Center for Immuno-Oncology, Center for Cancer Research, NCI, demonstrated the overall safety and clinically meaningful benefit observed with PRGN-2012, with a 51% complete response rate in patients treated at the highest dose.
Study results of the phase 1 portion were published in "The tumor microenvironment state associates with response to HPV therapeutic vaccination in patients with respiratory papillomatosis," Science Translational Medicine, 2023 Oct 25; 15(719):eadj0740, by Norberg...Schlom, Gulley...Sabzevari...Allen.
Phase 1/2 study results were presented by Dr. Norberg, on June 3, 2024, during ASCO's Annual Meeting, in a late-breaking oral presentation.
Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies.
Tumor-intrinsic loss of major histocompatibility complex class I (MHC- I) and aberrations in antigen processing machinery (APM) and interferon gamma (IFN-γ) pathways have been shown to play an important role in immune checkpoint blockade resistance. We demonstrated that the combination of entinostat and NHS- IL12 therapy elicits potent antitumor activity across αPD- 1/αPD- L1 refractory tumors. Our findings provide a rationale for combining the tumor-targeting NHS- IL12 with the histone deacetylase inhibitor entinostat in the clinical setting for patients unresponsive to αPD- 1/αPD- L1 and/or with innate deficiencies in tumor MHC- I, APM expression, and IFN-γ signaling. These findings were published in "Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies", Journal for ImmunoTherapy of Cancer, 2022; 10(6):e004561, by Minnar et al.