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Clin Cancer Res: Oncolytic virus therapy improves drug resistance against PD-1 treatment
▎ Clinical problems:
At present, intratumoral oncolytic virus therapy can reshape the tumor microenvironment through proinflammatory responses to overcome the drug resistance of PD(L)-1 monoclonal antibody treatment.
A study from Clin Cancer Res mainly explores the efficacy of ONCOS-102 (onlycolytic adenovirus expressing GM-CSF) and anti-programmed cell death protein 1 (PD-1) in the treatment of drug-resistant melanoma.
▎ Study Protocol:
This study mainly included patients with advanced melanoma who had previously undergone treatment with PD-1 blocker. All patients included in the study received intratumoral ONCOS-102 treatment, and the treatment regimen was divided into 3 doses (3×10 11 viral load) initial intratumoral injection [Part 1 (sequential treatment)] within the first week, or 4 doses of initial intratumoral injection and 8 intensive doses of intratumoral injection every 3 weeks [Part 2 (combination treatment)]. At the same time, starting from the third week, all patients received pembrolizumab (≤8 doses) every 3 weeks. The primary endpoint of the study was the safety of the drug, and also investigated objective response rate (ORR), progression-free survival (PFS), and immunologic activation in repeated biopsies.
▎ Mainly found:
1. A total of 21 patients (part 1, n=9; part 2, n=12) were tolerated for ONCOS-102 combined with pembrolizumab treatment. The severity of most adverse events (AE) was only mild or moderate. Among them, heat stroke (43%), chills (43%) and nausea (28%) were the most common AEs associated with ONCOS-102, and there was no dose-limiting toxicity.
2. solid tumor had ORR of 35%. In 53% of patients, tumor size reduction was observed in ≥1 non-injectable lesions, indicating that combined treatment has systemic effect.
3. In the injected tumor, the study found that the continuous expression of immune-related genes and T cell infiltration were related to the clinical benefits of patients. The persistence and efficacy of the virus in both injected and uninjected lesions support the use of a Part II dosing regimen for treatment in future studies and does not show additional toxicity.
▎ Outlook:
study found that in patients with advanced melanoma who are resistant to PD-1 treatment, not only are they tolerated with ONCOS-102 combined with pembrolizumab treatment very well, but they can also achieve objective relief. At the same time, ONCOS-102 can continue to promote the infiltration of T cells and (still persisted at week 9), especially cytotoxic CD8+ T cells, which in turn promotes clinical benefits of patients. Therefore, this study emphasizes the importance of future in-depth research on the combined treatment of ONCOS-102 and PD-1 blockers.
References:
[1]https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-2046/709574/Pilot-Study-of-ONCOS-102-and-Pembrolizumab
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This article was first published: Medical World Tumor Channel
Author: Dingchao Jingyao Group
Editor: Sweet
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