Oncolytic virus plus immunotherapy extends survival in recurrent glioblastoma
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Key takeaways:
- Although the objective response rate exceeded the prespecified control rate, it fell short of achieving the study’s primary efficacy endpoint.
- Most patients had stable disease or better.
The combination of intratumoral DNX-2401 and pembrolizumab appeared safe and provided “notable survival benefits” for select patients with recurrent glioblastoma, according to a study published in Nature Medicine.
The phase 1/phase 2 trial did not meet its primary efficacy endpoint of objective response rate; however, the combination conferred a 12-month OS rate of 52.7% — which exceeded the prespecified efficacy threshold of 20%, according to researchers.
“We are cautiously optimistic about the long-term clinical benefits for patients,” Gelareh Zadeh, MD, PhD, FRCSC, neurosurgeon, co-director of Krembil Brain Institute at Toronto Western Hospital and senior scientist at Princess Margaret Cancer Centre, said in a press release. “These drugs work by preventing cancer’s ability to evade the body’s natural immune response, so they have little benefit when the tumor is immunologically inactive — as is the case in glioblastoma.”
Background and methodology
Immune-mediated antitumoral responses induced by oncolytic viruses and augmented with checkpoint inhibition could improve outcomes for patients with glioblastoma, according to researchers.
The study evaluated the combination of intratumoral delivery of the oncolytic adenovirus DNX-2401 (DNAtrix) followed by pembrolizumab (Keytruda, Merck), an anti-PD-1 antibody, via IV among 49 patients with recurrent glioblastoma.
Overall safety and objective response rate served as the primary endpoints.
Results
Researchers noted no dose-limiting toxicities and the full dose combined treatment appeared to be well tolerated.
Researchers reported an ORR of 10.4% (90% CI, 4.2-20.7), higher than the prespecified control rate of 5% but statistically below the primary endpoint for efficacy.
However, the study did meet the secondary endpoint of OS at 12 months, with a rate of 52.7% (95% CI, 40.1-69.2) vs. the prespecified control rate of 20%.
Researchers reported median OS of 12.5 months (95% CI, 10.7-13.5). Objective responses resulted in longer survival (HR = 0.2; 95% CI, 0.05-0.87).
Most patients (56.2%; 95% CI, 41.1-70.5) derived clinical benefit, defined as stable disease or better. Three patients completed treatment with durable responses and remained alive at 45, 48 and 60 months.
Next steps
The study is one of few in recent years that have been favorable for patients with glioblastoma, according to researchers. Potential next steps include testing the combination therapy’s effectiveness against other treatments in a randomized clinical trial, they wrote.
“We are encouraged by these results, but there is still a lot of work ahead of us,” Farshad Nassiri, MD, PhD, a neurosurgery resident at University of Toronto, said in the release. “Our goal, as always, is to help our patients. That’s what motivates us to continue this research.”
References:
- Nassiri F, et al. Nat Med. 2023;doi:10.1038/s41591-023-02347-y.
- Study using novel approach for glioblastoma treatment shows promising results, extending survival (press release). Available at: https://www.newswise.com/articles/study-using-novel-approach-for-glioblastoma-treatment-shows-promising-results-extending-survival. Published May 16, 2023. Accessed May 16, 2023.
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