Robert Andtbacka, MD
Amid the rapid expansion of immunotherapy for a wide range of tumor types, oncolytic virus therapies are generating growing attention from researchers and pharmaceutical developers, raising the potential for a new class of immune-enhancing drugs.
More than 16 genetically modified virus therapies are being explored in clinical trials in the United States, either as monotherapy or in combination with other therapies, according to an industry report1
and a search of the ClinicalTrials.gov database. Although that number is outpaced by interest in the leading form of anticancer immunotherapy, the checkpoint blockade agents, and the emerging chimeric antigen receptor T-cell therapies, recent industry developments show heightened expectations for oncolytic viruses.
In February 2018, Merck agreed to pay $394 million to acquire Viralytics, an Australian company that is developing Cavatak (CVA21), a formulation of coxsackievirus type A21.2
The drug is being studied in combination with pembrolizumab (Keytruda), a PD-1 inhibitor that Merck developed, in melanoma, prostate, lung, and bladder cancers.
In another partnership that is moving forward, PsiOxus Therapeutics, based in the United Kingdom, announced that its oncolytic virus candidate, NC-348, has been approved for use in human trials, qualifying the company for a $15 million milestone payment from BristolMyers Squibb.3
PsiOxus previously received $50 million from Bristol-Myers to develop NG-348, which the company describes as an enadenotucirev virus, a genetically modified adenovirus, that is “armed” with 2 immunomodulatory membrane-integrated T-cell–engaging proteins.
As it stands now, the only FDA-approved oncolytic virus is talimogene laherparepvec (T-VEC; Imlygic), a form of herpes simplex virus type 1 (HSV-1) that has been genetically modified to express granulocyte-macrophage colony-stimulating factor. T-VEC was approved in 2015 for the locoregional treatment of recurrent, unresectable melanoma; it is injected into cutaneous, subcutaneous, and nodal lesions.4
T-VEC has proved to be a durable, well-tolerated therapy that has been effective as monotherapy in patients with no visceral to minimally visceral disease, Robert H.I. Andtbacka, MD, CM, a leading investigator of the drug, said during a presentation at the 14th Annual
International Symposium on Melanoma and Other Cutaneous Malignancies®
that Physicians’ Education Resource®
hosted in New York City in February. For patients with visceral disease, T-VEC combination therapies would be more effective, he said.
Oncolytic viral therapy exerts a direct cytotoxic effect on the tumor and appears to enhance the efficacy of other immunotherapies, said Andtbacka, who is a surgeon and investigator at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, where he also is an associate professor in the Division of Surgical Oncology.
“We know with these therapies that we can also use them to change the tumor microenvironment,” he said in an interview with OncologyLive®
. “In patients who don’t respond to PD-1 inhibition, we can use these intralesional therapies to change the tumor microenvironment and make some of these nonresponders into responders.”
Andtbacka pointed out 2 trials that, if successful, would lead to an expanded role for T-VEC in melanoma: a phase II study of neoadjuvant T-VEC with surgery versus surgery alone in patients with surgically resectable stage IIIb/c melanoma (NCT02211131) and the phase III MASTERKEY-265/KEYNOTE-034 study of pembrolizumab with or without T-VEC in patients with treatment-naïve, unresectable stage III or IV melanoma (NCT02263508).
Although T-VEC and other oncolytic virus therapies have been primarily studied in melanoma thus far, Andtbacka sees the potential for their utility in other tumor types, including liver metastases. “We really are expanding this into other cancers,” he said.