Abstract
Pembrolizumab with the oncolytic virus talimogene laherparepvec was effective in treating sarcomas.
Major Finding: Pembrolizumab with the oncolytic virus talimogene laherparepvec was effective in treating sarcomas.
Concept: In this phase II trial, many patients with advanced or metastatic sarcomas had partial responses.
Impact: Sarcomas may be responsive to combination therapy with immune checkpoint blockade and oncolytic viruses.
There are few treatment options for sarcomas, and even the treatments available have relatively low objective response rates (ORR). Treatment with pembrolizumab, a monoclonal antibody targeting PD-1, has shown some limited success in this tumor type, prompting further study of the drug in combination with agents that could augment its activity. To this end, Kelly and colleagues conducted a phase II clinical trial of pembrolizumab with talimogene laherparepvec—a genetically engineered oncolytic herpes virus that is injected directly into cancerous lesions to cause tumor-cell lysis and release of tumor antigens—in 20 patients with locally advanced or metastatic sarcoma. At the designated cutoff for ORR evaluation at 24 weeks following treatment initiation, the ORR was 30%; however, one patient with cutaneous angiosarcoma exhibited a delayed response at the 32-week mark, yielding an ORR of 35%. The substantial lag in response in this patient combined with the long median time to response (14.4 weeks) among all responding patients illustrates that prolonged treatment may be required to attain positive results with this treatment combination. No patients exhibited a complete response, and the median duration of response was 56.1 weeks. Notably, an antitumor response was observed at sites distant from the tumor injected with talimogene laherparepvec in patients with stage IV and recurrent locally advanced disease, demonstrating that this treatment may also be worth investigating in metastatic sarcoma. The combination treatment was generally well tolerated, with no treatment-related adverse events exceeding grade 3 and no treatment-related deaths occurring. Although the study had limitations, including its small size and lack of control arm, the findings presented warrant further exploration, and expansion of the study is ongoing.
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