Pilot Study of ONCOS-102 and Pembrolizumab: Remodeling of the Tumor Microenvironment and Clinical Outcomes in Anti-PD-1-Resistant Advanced Melanoma. Editorial Article uri icon

Overview

abstract

  • PURPOSE: Intratumoral oncolytic virotherapy may overcome anti-PD(L)-1 resistance by triggering pro-inflammatory remodeling of the tumor microenvironment. This pilot study investigated ONCOS-102 (oncolytic adenovirus expressing GM-CSF) plus anti-programmed cell death protein 1 (PD)-1 therapy in anti-PD-1-resistant melanoma. PATIENTS AND METHODS: Patients with advanced melanoma progressing after prior PD-1 blockade received intratumoral ONCOS-102 either as priming with 3 doses (3 × 1011 viral particles) during Week 1 [Part 1 (sequential treatment)] or as 4-dose priming and 8 booster doses every 3 weeks [Part 2 (combination treatment)]. From Week 3, all patients received pembrolizumab every 3 weeks (≤8 doses). The primary endpoint was safety. Objective response rate (ORR), progression-free survival, and immunologic activation in repeat biopsies were also investigated. RESULTS: In 21 patients (Part 1, n = 9; Part 2, n = 12) ONCOS-102 plus pembrolizumab was well tolerated: most adverse events (AE) were mild/moderate in severity. Pyrexia (43%), chills (43%), and nausea (28%) were the most common ONCOS-102-related AEs. There were no dose-limiting toxicities. ORR was 35% [response evaluation in solid tumors (RECIST) 1.1, irRECIST]. Reduction in size of ≥1 non-injected lesions observed in 53% patients indicated a systemic effect. In injected tumors, persistent immune-related gene expression and T-cell infiltration were associated with clinical benefit. Viral persistence and efficacy in injected and non-injected lesions without additional toxicity supported Part 2 dosing regimen in future studies. CONCLUSIONS: ONCOS-102 plus pembrolizumab was well tolerated and led to objective responses in patients with anti-PD-1-resistant advanced melanoma. ONCOS-102 promoted T-cell infiltration, particularly cytotoxic CD8+ T cells, which persisted at Week 9, driving clinical benefit. Further investigation of ONCOS-102 plus PD-1 blockade is warranted. See related commentary by Levi and Boland, p. 3.

publication date

  • January 4, 2023

Research

keywords

  • Melanoma
  • Tumor Microenvironment

Identity

PubMed Central ID

  • PMC9811163

Scopus Document Identifier

  • 85140581117

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-22-2046

PubMed ID

  • 36112545

Additional Document Info

volume

  • 29

issue

  • 1