Siteman Cancer Center served as a major, early clinical trial site for groundbreaking vaccine
In a major announcement, an experimental mRNA vaccine has been shown in global clinical trials to prevent melanoma from returning or spreading in high-risk melanoma patients when combined with the immunotherapy drug pembrolizumab, known commercially as Keytruda, and given after surgery.
The news is significant because more than 230,000 cases of melanoma are diagnosed in the U.S. each year. Up to 20% of invasive melanoma cases are considered high-risk at the time of initial diagnosis.
Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine served as a major and early clinical trial site for Phase II of the trial — known first as KEYNOTE-942 — which served as a “proof-of-concept” study to determine whether artificial intelligence could successfully be used to analyze a patient’s tumor for specific cancer mutations and then engineer a personalized mRNA vaccine to target those mutations. Findings from WashU Medicine physician-researchers at Siteman Cancer Center contributed integral information to the overall study, helping to advance development of the vaccine, said George Ansstas, MD, director of the Melanoma Program in WashU Medicine’s Division of Oncology and site principal investigator of the Phase II study at Siteman.
“Scientifically, it’s exciting to advance medicine in such meaningful ways,” he said. “Speaking as a physician, it’s highly rewarding to be able to offer cutting-edge treatments to our patients, whether in the form of clinical trials or newly approved therapies.”
Ansstas is also a professor of medicine at WashU Medicine and a research member at Siteman Cancer Center.
Following WashU Medicine and Siteman’s research contributions to the vaccine project, global Phase III clinical trials have now proven the effectiveness of the personalized combination treatment.
With more than 1,000 patients enrolled in the Phase III trial — known as INTerpath (Individualized Neoantigent Therapy) — researchers found that the mRNA-based individualized neoantigen therapy (INT), when used in combination with pembrolizumab after surgery, successfully kept patients diagnosed with high-risk melanoma cancer-free longer than pembrolizumab alone. The Phase III trial was overseen by two pharmaceutical companies that helped to develop the mRNA vaccine, Moderna and Merck.
“It is the first and only combination regimen to demonstrate statistically significant and clinically meaningful improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared to pembrolizumab alone for patients with completely resected Stage IIB-IV melanoma,” the companies stated in a joint announcement released Aug. 19.
The Phase III clinical trial offers hope that the mRNA vaccine combination therapy will be formally approved for use in more patients diagnosed with high-risk melanoma. It also opens the door wider to the development and use of personalized neoantigen vaccines to treat more cancers.
“Given the breadth and depth of our cancer vaccine expertise at WashU Medicine and Siteman, we are developing our own personalized therapies and advancing those developed elsewhere,” Ansstas said. “Improving treatments and outcomes for patients is a global effort. Being an important part of that is exciting — especially when you consider what it means for patients here at home.”
Learn more:
- Phase III clinical trial results: Merck and Moderna Announce Phase 3 INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA® Met Endpoints of Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS) in Patients With Completely Resected Stage IIB-IV Melanoma
- Phase II clinical trial results: Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study