INO-5151 / Inovio - LARVOL DELTA

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer. (PubMed, Clin Cancer Res) - P1 | "Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity. Pre-existing rather than treatment-induced immune activation was associated with clinical benefit across cohorts, highlighting the importance of baseline immune fitness."

Journal • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNFA

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer (Clin Cancer Res) - P1 | N=43 | PORTER (NCT03835533) | "43 patients enrolled (N = 14, 15, 14 in Cohorts A, B, C). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 10 (71%), 2 (13%), and 2 (14%) patients, respectively, with one Grade 5 TRAE in Cohort A. Composite response rates were 7% (1/14), 33% (5/15), and 7% (1/14). Across cohorts, 6-month disease control was associated with pre-existing memory/regulatory T cells, TNFα, and other inflammatory pathways....Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity."

P1 data • Castration-Resistant Prostate Cancer

PORTER: Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations (clinicaltrials.gov) - P1 | N=43 | Completed | Sponsor: Parker Institute for Cancer Immunotherapy | Active, not recruiting ➔ Completed | Trial primary completion date: May 2022 ➔ Oct 2022

Biomarker • IO biomarker • Trial completion • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Biomarker Correlates of Clinical Response with FLT3L/Nivo Backbone Treatment in the Multi-Cohort Phase 1 PORTER Platform Trial in Metastatic Castration-Resistant Prostate Cancer Patients (SITC 2022) - "Methods Two cohorts of the biomarker-rich PORTER platform trial tested a backbone combination of CDX-301 [FLT3L] and nivolumab. Cohort B added treatments to enhance endogenous immunity (stereotactic body radiation therapy/polyICLC). Cohort C included INO-5151, DNA vaccine expressing PSA/PSMA/IL-12 DNA plasmids...Further work to integrate these findings with tumor imaging and genomic data is ongoing. Overall, the joint analysis of the two cohorts involving FLT3L + nivolumab highlights the power of a platform study to rapidly identify common biomarkers of clinical response and/or resistance and simultaneously interrogate treatment effects of cancer-specific immunotherapy combinations."

Biomarker • Clinical • IO biomarker • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD63 • CD8 • IL12A • LAMP3 • PD-1

Clinical and Pharmacodynamic Biomarker Results from PORTER, a multi-cohort Phase 1 Platform Trial of Combination Immunotherapy for Metastatic Castration-Resistant Prostate Cancer Patients (SITC 2022) - "Three cohorts were enrolled A) bempegaldesleukin/nivolumab, B) stereotactic body radiation therapy (SBRT)/CDX-301 (FLT3L)/poly-ICLC/nivolumab, and C) CDX-301/INO-5151 (DNA vaccine encoding PSA/PSMA/IL-12)/nivolumab. Conclusions This platform study design demonstrated the feasibility and efficiency of iteratively testing distinct immunotherapy combinations with comprehensive biomarker assessment in patients with mCRPC. While neither cohort A nor C were expanded due to insufficient clinical activity, the clinical responses seen with SBRT/FLT3L/polyICLC/nivolumab suggest sufficient clinical benefit that may warrant additional investigation, particularly the contribution of radiation to the responses observed."

Biomarker • Clinical • IO biomarker • P1 data • PK/PD data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IFNG • IL12A

PORTER: Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Parker Institute for Cancer Immunotherapy | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2023 ➔ Oct 2022

Biomarker • Enrollment closed • IO biomarker • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PORTER: Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: Parker Institute for Cancer Immunotherapy | Trial primary completion date: Mar 2022 ➔ May 2022

Biomarker • IO biomarker • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Dr. Shore on Challenges with ADT in Recurrent Prostate Cancer (OncLive) - "Neal D. Shore, MD, FACS...discusses challenges with androgen deprivation therapy (ADT) in recurrent prostate cancer....This unmet need served as the basis for a phase 1/2, open-label, multicenter study that assessed INO-5150, a DNA-based immune therapy, with or without INO-9012, in patients with biochemically recurrent prostate cancer, Shore concludes."

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