ASH: Allogene's off-the-shelf CAR-T posts 60% response rate in fiercely competitive BCMA field

Allogene Therapeutics has linked its off-the-shelf anti-BCMA CAR-T cell therapy to a 60% response rate in a phase 1 trial. The candidate is up against autologous cell therapies that have set the efficacy bar high, but Allogene has off-the-shelf advantages and levers to pull to further improve outcomes.

The original release of data on ALLO-715 last month was overshadowed by news of a death in the phase 1 study. Investigators deemed the death related to progressive myeloma and conditioning regimen, but Allogene’s stock price fell nonetheless. Allogene arrived at the annual meeting of the American Society of Hematology (ASH) with updated data to make its case for ALLO-715.

South San Francisco-based Allogene said it is very pleased with the data. The trial shows Allogene can manufacture ALLO-715 and safely administer it. Efficacy, while short of the bar set by autologous rivals, is a starting point that may be improved on as Allogene moves through and beyond the dose-escalation trial. 

Allogene focused on the 10 multiple myeloma patients in the dose-escalation trial who received 320 million cells. At that dose level, 60% of patients responded to the therapy. Forty percent of patients experienced very good partial responses or better. The cohort is split between patients who received high or low levels of Allogene’s anti-CD52 antibody ALLO-647 in the lymphodepletion regimen, but the numbers are too small to draw firm conclusions about the effect of changing the dose. 

“The efficacy signal met our expectation, and the responses may deepen over time given the short follow-up time,” analysts at Jefferies wrote in a note to investors. “The KOL on ALLO's ASH webinar feels the first allogeneic BCMA-CART data are encouraging, and highlights the depth of the response, which is manifested by MRD negative status, as a critical factor for predicting remission.” 

All five of the evaluable very good partial response or better patients were minimal residual disease negative. That data point suggests ALLO-715 may be able to hold its own against autologous CAR-Ts in development at Bristol Myers Squibb and Johnson & Johnson, although other aspects of the data are currently less favorable for Allogene.

J&J used ASH to share updated data on its Legend Biotech-partnered anti-BCMA cell therapy, linking the asset to near-100% response rate. Most responses to the cell therapy are complete. Allogene is working to improve on its efficacy, including by enrolling patients at higher doses. Work to evaluate ALLO-715 in combination with SpringWorks’ investigational gamma secretase inhibitor nirogacestat and to move a new TurboCAR BCMA candidate into the clinic are advancing, too. 

It is possible Allogene can be competitive even if its BCMA therapies fall short of the bar set by their autologous rivals. The median time from enrollment to the start of therapy was five days. Autologous candidates cannot match that turnaround. That has implications for patients. 

“The KOL points out that up to 10 weeks of wait time and associated infection risks from bridging therapies make autologous BCMA-CART less than ideal for the subgroup of patients with hyper progressive diseases,” the Jefferies analysts wrote.

Allogene’s allogeneic approach carries its own theoretical risks, but the biotech is yet to see a case of graft-versus-host disease in the phase 1. Almost half of the 29 patients in the full data set experienced cytokine release syndrome, a common CAR-T complication, but all the cases were grade 1 or 2 in severity. The Jefferies analysts said “safety appears favorable to [Allogene’s] autologous peers although the patient numbers are small.”