LUMINOS-102: PVSRIPO with or without immune checkpoint blockade in unresectable anti-PD-1 refractory melanoma
Wang D, Lance Cowey C, Pisick E, Kirkwood J, Corum D, Morris SR, Kelly AT, Sorrentino J, Mixson L, Dickinson A, Garrett Nichols W, and Najjar YG. LUMINOS-102: PVSRIPO with or without immune checkpoint blockade in unresectable anti-PD-1 refractory melanoma. Pigment Cell Res 2022; 35(1):150-151.
Pigment Cell Melanoma Res
PVSRIPO, a novel viral immunotherapy, infects solid tumors and antigen-presenting cells (APCs) via CD155. Infection is lethal in malignant cells, but nonlethal infection of local APCs yields type I/III interferon-dominant induction with subsequent anti-tumor T-cell priming and activation. A phase 1 dose-escalation study (Beasley 2021, JITC) showed PVSRIPO was well tolerated and demonstrated anti-tumor activity in both injected and noninjected lesions in patients (pts) with αPD-1-refractory melanoma. In preclinical models, PVSRIPO-mediated immune activation upregulated the PD-1/L1 pathway, leading to greater anti-tumor response with PVSRIPO and αPD-1 combination therapy. Taken together, these data suggest PVSRIPO is active in αPD-1-refractory melanoma and that PVSRIPO±αPD-1 therapy warrants further clinical investigation. LUMINOS-102 (NCT04577807) is an ongoing multi-center, open-label, randomized phase 2 study investigating the efficacy, safety, and pharmacodynamic effects in the tumor microenvironment following PVSRIPO±αPD-1 therapy in pts with αPD-1-resistant, unresectable, non-uveal melanoma. A safety run-in cohort of 6 pts to characterize PVSRIPO injection in ≥6 lesions/cycle or maximum dose of 6x108TCID50 has fully enrolled; 1:1 randomization of 50 participants to receive PVSRIPO (Arm 1) or PVSRIPO+αPD-1 (Arm 2) is ongoing. Stratification factors include time since last αPD-1 dose and baseline LDH level. Crossover (Arm 1 to 2) is allowed upon confirmed progression, SD at 26 weeks, or PR ≥6 mos. Primary endpoints include safety, ORR per RECIST 1.1, and change from baseline in CD8+ tumor-infiltrating lymphocytes and PD-L1 expression. Key secondary endpoints include DOR, DCR, PFS, and OS. Exploratory endpoints include ORR via iRECIST and additional biomarker analysis evaluating the immune activation phenotype of PVSRIPO.