By: Arlene Weintraub
The big news about chimeric antigen receptor T-cells (CARTs) at the American Society of Clinical Oncology meeting that just concluded in Chicago is that there was no earth-shattering news. Some analysts feared that predictions of FDA approvals as early as 2017 would prove overly optimistic for the technology, which involves removing immune-boosting T-cells from patients, engineering them to target their specific cancers, then re-infusing them. But at ASCO, the three leaders in the space—Novartis (led by its collaborator, the University of Pennsylvania), Kite Pharma and Juno Therapeutics—presented data on their CART programs in blood cancers that clearly showed the cells are still performing well in clinical trials.
Here are some of the highlights: Juno reported that in a phase I/II trial of its CART, JCAR014, in 34 patients with acute lymphoblastic leukemia (ALL) all achieved complete remissions, and pre-treating patients with a two-drug chemo cocktail beforehand seemed to improve the response for some. Kite reported that three out of seven patients with aggressive non-Hodgkin lymphoma (NHL) were still in remission nine months after receiving its CART, KTE-C19. And University of Pennsylvania scientists reported a 79% response rate at 12 months in children with ALL who received CTL019, which they are developing with Novartis, and 15 of 30 adult patients with NHL who got the treatment experienced complete remissions.
In addition to moving their therapies into late-stage development in blood cancers, all three companies are looking seriously at a variety of techniques for optimizing the production of CARTs and the methods of administering them to patients. And they’re all actively looking for ways to extend the technology to other cancers. “Are solid tumors something that CARTs will be amenable to? We think they can be,” says Usman Azam, global head of the cell and gene therapies unit at Novartis. “Solid tumors present a lot of challenges, but that’s the next wave of innovation.”
One big push in CART development is to try to improve the ability of the cells to grow and to persist in the bloodstream after they are infused into patients. Towards that end, Juno has been investigating a pre-treatment regimen of two chemo drugs, fludarabine and cyclophosphamide. Early results suggest that a low dose of the cocktail seems to improve how the CARTs grow and persist, says Steve Harr, Juno’s chief financial officer and head of corporate development. “One of the insights we had about a year and a half ago was that the clinical benefit that we saw with these CART cells directly corresponded with how well they grew early and how long they lasted once they were infused in the body,” Harr says. “We’re seeing some significant improvements in both the cell expansion and persistence since we changed the way we treat patients before they get their CART cells.”
What’s more, Juno reported at ASCO that 16 out of 20 patients in one trial who received the low-dose chemo before their CART doses were treated in outpatient centers and six didn’t have to return to the hospital to be treated for side effects. Although the results are early, the company believes it is finding better ways to pick the optimal CARTs to be infused, and to predict and manage side effects, most notably cytokine release syndrome, a particularly scary immune response that has sent some patients in the clinical trials into intensive care. “There have been questions about how T-cells will be able to be delivered to broader patient populations,” Harr says. “There is monitoring that can be done to predict which patients will get sicker, and 30% of them are never hospitalized.” Juno’s rivals are also investigating various methods for predicting which patients are most likely to suffer adverse events and for preventing and treating those side effects.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.