Title

LUMINOS-102: PVSRIPO with or without immune checkpoint blockade in unresectable anti-PD-1 refractory melanoma

Document Type

Conference Proceeding

Publication Date

12-30-2021

Publication Title

Pigment Cell Melanoma Res

Abstract

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.

Volume

35

Issue

10

First Page

150

Last Page

151

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