Allogene Therapeutics has reported phase 1 data on its solid tumor CAR-T, linking the off-the-shelf cell therapy candidate to a 33% response rate but also three deaths in heavily pretreated cancer patients.
The trial had enrolled 39 patients as of the data cutoff. All the participants received a single infusion of the anti-CD70 CAR-T ALLO-316. Allogene included 26 patients with CD70-positive renal cell carcinoma in the efficacy analysis. The biotech presented data, including one dose-limiting toxicity (DLT), last year and shared updated safety and efficacy results Thursday.
Allogene reported three grade 5 treatment-related adverse events and one new DLT, cardiogenic shock. The patient with cardiogenic shock was one of the three people who died of treatment-related adverse events.
Another patient died of sepsis from multidrug-resistant Klebsiella pneumoniae. That patient had a prior episode of muscle abscess and bacteremia from the same multidrug-resistant Klebsiella. Allogene called the third death a “failure to thrive in a participant 16 months after treatment with ALLO-316.” The patient had stable disease at Month 12 and no interval scans to evaluate disease status prior to death.
Allogene CEO David Chang, M.D., Ph.D., discussed the deaths on an earnings call Thursday in response to questions from analysts. Chang said “there is never a simple adverse event” in oncology patients with advanced metastatic tumors. The events are “very much confounded by the underlying disease,” the CEO said, and, in phase 1 CAR-T trials, by the different doses and lymphodepletion regimens that are tested.
The biotech reported a confirmed response rate of 33% and best overall response rate of 50% in six heavily pretreated patients with high CD70 expression. Allogene defined high CD70 expression as a tumor proportion score greater than 50%, a threshold Chang said “represents the majority of patients.” The biotech was bullish about the data.
“Given the number of previous therapies these patients have been on, most of which were in combination, I can't overstate how meaningful this data is: a single infusion that generates responses in patients with advanced disease and also yields what we would call a treatment break,” Zachary Roberts, M.D., Ph.D., chief medical officer of Allogene, said on the earnings call.
Roberts believes the antitumor activity is partly attributable to Allogene’s CD70 Dagger technology, which the biotech is pitching as a way to enable robust cell expansion and persistence with standard lymphodepletion. The Dagger technology is central to Allogene’s goal of reducing or eliminating the need for lymphodepleting chemotherapy in recipients of its autoimmune cell therapy candidate ALLO-329.
The fact Dagger is common to ALLO-316 and ALLO-329 led one analyst to ask Allogene whether the deaths have implications for the autoimmune program. Chang said Dagger enhances the pharmacodynamic effect of CAR-T, so, to some extent, the technology is implicated in the adverse events. However, the CEO pushed back on the idea that the safety findings have implications for the autoimmune program.
“These are very heavily pretreated patients, really running out of options and usually in that kind of situation they are pretty sick patients. So, yes, these events did occur, but trying to read through that to what may happen in autoimmune patients ... I don't think there is much that we can read through,” Chang said.
Allogene is aiming to include about 20 patients in the phase 1b ALLO-316 expansion cohort and share additional data from that part of the study in mid-2025. The durability of responses is an outstanding question that will be answered as the data mature.