The two FDA-approved CAR-T treatments for blood cancers, Novartis’s Kymriah and Kite/Gilead’s Yescarta, have improved the prognosis for many patients, but they have one key drawback: They are made from patients’ own immune cells in a cumbersome process that can take weeks. That’s one of the reasons companies developing “allogeneic,” or off-the-shelf CAR-Ts—made from donor cells and designed to be given to any patient—have generated enthusiasm from oncologists and investors.

Now, one of those companies, Allogene, is unveiling the first evidence that its off-the-shelf CAR-T may have promise in treating some patients with lymphoma, though the data is admittedly immature. Nevertheless, it’s bound to attract plenty of interest given the company’s pedigree—it was co-founded by Kite’s Arie Belldegrun, who raised $420 million in private financing for Allogene before picking up $288 million in an initial public offering in September 2018.

In data released today for the virtual meeting of the American Society of Clinical Oncology (ASCO), Allogene reported an overall response rate of 78% in a trial of the CAR-T ALLO-501 combined with the antibody ALLO-647 in patients with non-Hodgkin lymphoma who had failed previous therapies. Among the nine patients who have been treated so far, three had complete responses and four had partial responses. Three of the initial responders eventually relapsed within six months, the company reported.

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“There were some important hypotheses that we wanted to show, one of which was that allogeneic CAR-T cells can be successfully manufactured and administered safely,” Allogene co-founder and CEO David Chang, M.D., Ph.D., told FierceBiotechResearch. “The second is that they can expand and carry out anti-tumor activities. This phase 1 study begins to address those hypotheses.”

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During the trial, patients receive chemotherapy and ALLO-647 as the “lymphodepletion” stage, during which some of their own T cells and lymphocytes are destroyed so the CAR-T cells can expand and begin to attack the cancer. They then receive ALLO-501, the CAR T that Allogene derived from a healthy donor and engineered to target CD19, an antigen on the surface of some blood cancer cells.

ALLO-501 was also engineered to disrupt a gene called TCR alpha, the goal of which was to reduce the risk of graft-versus-host disease (GvHD)—a rejection of the donor cells. There was no graft vs. host disease among the treated patients in the trial, Allogene reported. “We’re very excited that safety issues were either unremarkable or easily manageable,” Chang said.

One of the major concerns with the personalized CAR-T treatments that are on the market is they can cause a dangerous immune reaction called cytokine release syndrome (CRS). Two of the patients in Allogene’s trial experienced CRS, and a third suffered neurotoxicity. The side effects resolved without the need for treatment, but no doubt safety will be a major focus of analysts when data from larger trials is reported.

Allogene is also facing competition from other companies developing off-the-shelf CAR-T treatments, including Precision BioSciences and CRISPR Therapeutics, both of which also have CD19-directed treatments for non-Hodgkin lymphoma in phase 1 trials. Analysts are expecting those companies to release data from the trials by the end of the year.

Chang says all of the players in the off-the-shelf CAR-T space will be under pressure to show not just safety, but efficacy that rivals that of personalized cell treatments like Kymriah and Yescarta. “The response rate and the durability of the response has to be somewhat similar,” Chang said. The studies, he added, will need to show “durable responses that go on for several months.”

The ongoing trial of ALLO-501 is comparing three different doses of the CAR-T cells and two doses of ALLO-647. Chang declined to provide details about whether the size of the doses corresponded to the likelihood of response, but Allogene plans to release additional data from the trial during the second phase of the virtual ASCO conference, including results seen in patients who were treated with higher doses of ALLO-647.

The initial results from the phase 1 provide solid proof-of-concept that administering CAR-T cells from unrelated donors can be a viable strategy for treating non-Hodgkin lymphoma, Chang said. “If we can provide a ready-made product off-the-shelf that can be used when the patients are available, that can provide a meaningful difference to them,” he said. “We’re very excited about the results and looking forward to providing more comprehensive details at the ASCO presentation only two weeks from now.”



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