Abstract P045: LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO and PVSRIPO in combination with anti-PD-1/L1 checkpoint inhibitors in patients with advanced solid tumors
Authors: Inman Brant A. , Milowsky Matthew I. , Pruthi Raj S. , Posner Marshall , Polasek Melissa J. , Morris Shannon R. , Mixson Lori , Orr Kristin , Woodson Elizabeth M. H. , Kelly Andrea T. , Nichols W. Garrett , Balar Arjun V. 
Published: December 2021

Abstract
Background: PVSRIPO, a novel intratumoral viral immunotherapy, infects cells via CD155, which is widely expressed on solid tumors and antigen-presenting cells (APC). Infection is lethal in malignant cells, but a unique, activating, nonlethal infection of local APCs yields type-I/III interferon (IFN)-dominant inflammation with subsequent anti-tumor T-cell priming and activation. In preclinical models, PVSRIPO-dependent inflammation upregulated the PD-1/L1 pathway, and greater anti-tumor response was observed with PVSRIPO + anti-PD-1/L1 (αPD-1/L1). Promising clinical activity with PVSRIPO monotherapy was observed in patients (pts) with recurrent glioblastoma and advanced αPD-1–refractory melanoma (Desjardins 2018 NEJM, Beasley 2021 JITC). Collectively, these results warrant further clinical investigation of PVSRIPO ± αPD-1/L1. Trial design, objectives, and eligibility criteria: LUMINOS-103 (NCT04690699) is a phase (Ph) 1/2, open-label, multi-center, single-arm basket trial evaluating repeat administration of PVSRIPO ± αPD-1/L1 in adults with solid tumors. Trial objectives are to assess the safety and tolerability of PVSRIPO monotherapy in each cohort in Ph 1 and the safety, tolerability, and antitumor efficacy of PVSRIPO + αPD-1/L1 in each cohort in Ph 2. The first two study cohorts include pts with muscle-invasive bladder cancer being treated in the neoadjuvant setting (A) and pts with metastatic bladder cancer being treated in the 1st/2nd line setting (B); these cohorts have been described previously (Inman 2021 Virtual AACR Annual Meeting). Cohort C includes pts with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) being treated in the neoadjuvant setting; Cohort D includes pts with recurrent/metastatic HNSCC with a PD-L1 Combined Positive Score ≥1 being treated in the 1st line setting. Eligibility: HNSCC pts must have histologically or cytologically proven SCC of the oral cavity, oropharynx, hypopharynx, or larynx. All pts must have prior and boosted PV immunization and tumors amenable to injection and biopsy. Key exclusion criteria: Requirement for oxygen supplementation, systemic or intratumoral therapy ≤6 months prior to the first dose of study drug, CNS metastases requiring immediate treatment, systemic immunosuppressive medications ≤4 weeks prior to the first dose of study drug, and severe active comorbidities. Pts who are HIV+, HBV+ or HCV+ are eligible provided they meet certain criteria. Endpoints: Primary endpoints include safety (all), tolerability (all), surgical complication rate (A, C), pathologic treatment effect/response (A, C), and objective response rate (B, D). Secondary endpoints include overall survival (all), pathologic downstaging and relapse-free survival (A, C), duration of response and progression-free survival (B, D), and assessment of tumor/blood biomarkers (all).
Citation Format: Brant A. Inman, Matthew I. Milowsky, Raj S. Pruthi, Marshall Posner, Melissa J. Polasek, Shannon R. Morris, Lori Mixson, Kristin Orr, Elizabeth M. H. Woodson, Andrea T. Kelly, W. Garrett Nichols, Arjun V. Balar. LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO and PVSRIPO in combination with anti-PD-1/L1 checkpoint inhibitors in patients with advanced solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P045.