Abstract CT242: LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO in patients with advanced solid tumors
Authors: Inman Brant A. , Balar Arjun V. , Milowsky Matthew I. , Pruthi Raj S. , Polasek Melissa J. , Morris Shannon R. , Mixson Lori , Orr Kristin , Woodson Elizabeth M. , Kelly Andrea True , Nichols Garrett 
Published: July 2021

Abstract
Background: The recombinant poliovirus (PV):rhinovirus chimera, PVSRIPO, is a novel non-neurovirulent, intratumoral (IT) immunotherapy showing promising clinical activity in patients (pts) with recurrent glioblastoma and advanced anti-PD-1 refractory melanoma (Desjardins 2018 NEJM, Beasley 2020 SITC). PVSRIPO targets CD155 (PV receptor), expressed on most solid tumors (including bladder cancer [BC]) and antigen presenting cells (APCs) of the tumor microenvironment (TME). PVSRIPO infection results in inflammatory-mediated destruction of tumor cells but non-lethal lingering infection in TME APCs. This leads to a type-I/III interferon-dominant inflammation and ultimately, tumor antigen-specific T cell activation and recruitment (Brown 2017 Sci Transl Med), potentiated by immunologic recall to intratumoral replicating virus via prior vaccination. Induction of type-1 IFN dominant inflammation and compensatory activation of the PD-1:PD-L1 immune checkpoint (IC) pathway support investigation of PVSRIPO in combination with PD-1/L1 IC inhibitors. PVSRIPO+anti-PD-1 therapy resulted in greater anti-tumor response than either agent in immunologically cold mouse tumor models. Trial design, objectives, and eligibility criteria: LUMINOS-103 (NCT04690699) is a phase 1/2, open-label, multi-center, single-arm basket trial evaluating repeat administration of PVSRIPO (2×108 TCID50/mL)±anti-PD-1/L1 therapy in adults with solid tumors. Trial objectives are to evaluate the safety, tolerability, and anti-tumor activity of the combination in pts with solid tumors, beginning with muscle invasive bladder cancer (MIBC). The first arm will include pts in 2 cohorts: MIBC undergoing cystectomy (A); and unresectable locally advanced/metastatic BC (B). Safety/tolerability of PVSRIPO IT injections via cystoscopy will be evaluated in phase 1, Cohort A, and proceed to phase 2, where PVSRIPO+anti-PD-1/L1 therapy will be assessed in both cohorts. Eligible BC pts must refuse/be ineligible for cisplatin (A) or platinum-based therapy (B), have prior and boost PV immunization, and have measurable tumors (B) amenable to injection. Key exclusion criteria: other anti-cancer therapies ≤3 weeks, CNS metastases requiring active radiotherapy or steroids ≤14 days, systemic immunosuppressives ≤4 weeks, and severe active comorbidities. Endpoints: Primary endpoints include safety and tolerability and pathologic complete response (A) or overall response rate (B). Secondary endpoints: overall survival (both cohorts); for A, pathologic downstaging (p≤T2) and relapse-free survival; for B, duration of response and progression-free survival. Exploratory endpoints: assessment of tumor/blood biomarkers; measurement of disease by itRECIST. The trial will open US enrollment ≈ Q2 2021; results will inform later-stage trials in promising indications.
Citation Format: Brant A. Inman, Arjun V. Balar, Matthew I. Milowsky, Raj S. Pruthi, Melissa J. Polasek, Shannon R. Morris, Lori Mixson, Kristin Orr, Elizabeth M. Woodson, Andrea True Kelly, Garrett Nichols. LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT242.