Immuno-oncology stole the spotlight again at this year’s annual meeting of the American Society of Clinical Oncology (ASCO). Recent data showed that Merck’s checkpoint inhibitor Keytruda cuts the risk of death significantly in newly diagnosed lung cancer patients and Bristol-Myers Squibb made a case for Opdivo combos.
Earlier-stage I-O treatments were highlighted at the conference too, including a modified form of poliovirus originally developed at Duke University. The closely watched virus is now in clinical trials in glioblastoma, but preclinical results released at ASCO showed it may also help patients with hard-to-treat breast tumors.
The modified virus, called PVSRIPO, was designed to infect and kill tumor cells, and to initiate a further attack by cancer-killing immune cells in the body. During ASCO, Duke scientists published an abstract of a study they performed in mice, investigating whether PVSRIPO, combined with drugs that inhibit the immune checkpoints PDL1 or PD1, would help control the growth of breast tumors. PD1 is also the mechanism of action in Keytruda and Opdivo.
The Duke team discovered that combining a version of PVSRIPO made for mice with a checkpoint inhibitor significantly slowed breast tumor growth, according to the abstract. The combination was more effective than checkpoint inhibition alone.
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The researchers wanted to try the virus in breast cancer because the hard-to-treat triple-negative form of the disease is known to express large amounts of a protein called CD155. Last year, the Duke team announced their discovery that PVSRIPO invades glioblastoma tumors by attaching to CD155 on the surface of cancer cells. That allows the virus to kill some glioblastoma cells directly, which then triggers an “alarm” in the immune system, they said. That process seems to be what makes cancer cells vulnerable to an ongoing immune attack.
Duke’s research on polio as a potential weapon against cancer was launched into the spotlight in 2015 by the hit CBS show 60 Minutes, even though only a handful of glioblastoma treatments had been treated with modified form of the virus at the time. Duke neurosurgery professor Matthias Gromeier, M.D., who was one of the researchers featured in that segment, said last year that discovering CD155’s role in making the virus effective against cancer would be key to the further development of PVSRIPO—and to figuring out how to combine it with other therapies to improve patient survival.
PVSRIPO is being developed by Duke spinout Istari Oncology. The treatment is currently in a phase 2 study in patients with malignant glioma, either alone or combined with chemotherapy. There are also several earlier trials underway in adults and children with glioma, and the company is planning a phase 1 trial of the virus combined with anti-PD1 therapy in glioblastoma.
Istari is now planning a phase 1 trial of PVSRIPO in patients with HER2 negative breast cancer, according to the abstract published at ASCO. The study will be designed to determine if combining the modified poliovirus with an anti-PDL1 drug will help control tumor growth.