In this new age of cancer immunotherapy, two versions have been approved. The first are checkpoint inhibitors, which have begun to change the way skin, lung, and other cancers are treated. The second are CAR-T cell therapies, which have shown promise in blood cancers. A third type of cancer immunotherapy is just now reaching clinical studies, and some early returns are in.
Neon Therapeutics (NASDAQ: [[ticker:NTGN]]) today is disclosing results from an early study of a personalized vaccine that, for manufacturing, first requires extracting a sample of a patient’s own tumor. The process currently takes a few months and adds an extra degree of difficulty to a field that is already testing the cutting edge of biology.
The results “look promising” but come with plenty of caveats, according to the study’s lead investigator. “I wouldn’t say I’m convinced that this has activity. We don’t know,” said Patrick Ott, the clinical director of Dana Farber Cancer Institute’s Center for Immuno-Oncology in Boston. (Neon spun out of research at Dana Farber. Ott did some consulting for Neon, but says he has no current ties to the company.)
The Phase 1 trial of Neon’s NEO-PV-01 recruited 82 patients with various solid tumors. They first received the Bristol-Myers Squibb (NYSE: [[ticker:BMY]]) immunotherapy nivolumab (Opdivo), then 12 weeks later received the Neon vaccine. The top-line results of the study showed about 40 percent of the participants—those with advanced melanoma, a type of skin cancer—did quite well based on how long their tumors were kept from growing. Others, with bladder and lung cancers, also did well.
But there are several reasons to temper enthusiasm. Among them: The staggered dosing of Opdivo and NEO-PV-01 makes it difficult to tell if good results are from the vaccine or a delayed effect of Opdivo, said Ott.
Another reason is that the regimen hasn’t been studied head-to-head against a checkpoint inhibitor—a test that would provide more definitive answers.
It’s also unclear if the combination will help patients live longer, the gold standard for a cancer medicine. And other immunotherapy combinations have showed early promise only to flounder later.
Neon CEO Hugh O’Dowd, a former Novartis (NYSE: [[ticker:NVS]]) oncology executive, called it “the first demonstration of clinical activity” for this kind of cancer treatment, which is called a neoantigen vaccine.
Neon has competitors in the neoantigen vaccine field, among them Gritstone Oncology (NASDAQ: [[ticker:GRTS]]), and Genocea Biosciences (NASDAQ: [[ticker:GNCA]]). Messenger RNA drug developers Moderna (NASDAQ: [[ticker:MRNA]]) and BioNTech are in the mix with different methods, as are Advaxis (NASDAQ: [[ticker:ADXS]]), Agenus (NASDAQ: [[ticker:AGEN]]), and others. (This article by consulting firm Back Bay Life Science Advisors takes a deeper look at the field.)
Neoantigen vaccines contain a cocktail of engineered neoantigens—proteins that form on the surface of tumor cells as they mutate. These neoantigens can drive tumor growth, but they also serve as genetic fingerprints that the immune system can recognize if it’s tuned properly.
Some research in recent years has linked the presence of neoantigens to better responses to immunotherapy. This paper published in the New England Journal of Medicine in 2014, for instance, showed that a melanoma patient’s response to checkpoint inhibitors depended on the presence, and abundance, of neoantigens.
Very Complicated
Logistical challenges await Neon and other neoantigen vaccine developers as they advance. NEO-PV-01 involves a complex process: sample a patient’s tumor, use DNA sequencing technology to identify the neoantigens, and use those insights to develop a vaccine personalized to each patient. Another complex cancer treatment, known as CAR-T, has struggled commercially and takes two to three weeks to produce. O’Dowd says it currently takes
