When Allogene reported a 78% response rate to its off-the-shelf CAR-T two weeks ago, the data came with the caveat that it only applied to nine lymphoma patients in an early clinical trial. Now, Allogene is unveiling details on all 22 patients treated so far, and though the response rate isn’t quite as impressive—63% overall—the details could generate some excitement among Wall Street analysts.
Of the 22 patients treated with the Allogene’s CD19-directed CAR-T, ALLO-501, plus its antibody ALLO-647, 19 were analyzed for efficacy. Seven had complete responses and five had partial responses. Nine of the 12 responders still had not relapsed after a median follow-up period of nearly four months. The company released the data at the virtual meeting of the American Society of Clinical Oncology (ASCO).
But the complete response rate was 50% among patients who received higher doses of ALLO-647, which was used to deplete their own T cells and lymphocytes so the CAR-T cells could expand. And when one patient progressed two months after receiving the cells, the company’s investigators decided to try a second CAR-T dose along with a higher dose of ALLO-647.
It worked: That person started to respond and is still well today, said Allogene co-founder and CEO David Chang, M.D., Ph.D., in an interview with FierceBiotechResearch.
“Given that patient had a partial response but never went to complete remission, we wanted to test whether re-dosing would work” along with a higher dose of ALLO-647, Chang said. Although the strategy was tried in only one patient, Chang added, it’s an indication that boosting the dose of ALLO-647 “may give a little bit of a deeper response.”
Given that ALLO-647 is a key element of Allogene’s strategy for building a market for off-the-shelf CAR-T cells, analysts have been waiting for details about how the dosing of the antibody affects response. After Allogene reported data on a smaller patient sample two weeks ago, Jefferies analyst Biren Amin noted in a report to clients that three out of seven responders to ALLO-501 eventually relapsed, but the analysts "think this can improve with a higher dose of lymphodepletion” with ALLO-647.
While Allogene is facing competition from other companies developing off-the-shelf CAR-T treatments, its biggest competitors right now are the two FDA-approved personalized CAR-T therapies: Novartis’s Kymriah and Gilead Sciences' Yescarta, which are also directed at CD19.
Three of the patients in Allogene’s trial had failed previous treatments with personalized CAR-Ts. Interestingly, they also did not respond to ALLO-501, the company said.
Chang said Allogene doesn’t know why those patients’ lymphoma was resistant to different types of CAR-T treatments, but the company will need to figure that out so it can determine which patients are most likely to respond to ALLO-501. “There is something different about those patients’ tumors, and we will be looking at them carefully to better understand what really happened to those patients,” Chang said.
It’s possible all three patients had defects in the “death-inducing pathway,” the signaling system in the body that prompts cancer cells to die, Chang added.
Safety is another issue facing off-the-shelf CAR-T cells. ALLO-501 was engineered to reduce the risk of rejection, or graft-versus-host disease, and no incidences of that side effect occurred in the trial, Allogene said. Another concern is cytokine release syndrome, a dangerous immune response. That occurred in 32% of the patients, Allogene said, but it was “mild to moderate” and resolved within a week.
There were some infections, which were also resolved, Allogene said. Furthermore, Chang said, “as we analyze the data, we don’t see any trend indicating that the adverse event profile is worse in patients receiving a higher dose of 647.”
The company also said today it initiated a clinical trial of an improved version of ALLO-501 that’s designed to eliminate a “recognition domain” for Rituxan—a drug often used to treat patients with non-Hodgkin lymphoma. That domain, Chang explained, can act as a “kill switch” for the CAR-T cells. If the trial is successful, the enhanced version of ALLO-501 will be brought into phase 2, the company said.
Jefferies’ Amin estimates ALLO-501 will reach peak sales of $842 million in 2030. The initial small set of data released at ASCO prompted him to raise his price target on Allogene from $37 a share to $45. The stock was trading at $46 prior to the release of the expanded data set Friday morning.