Allogene gets green light for pivotal CAR-T trial, starts industry's first off-the-shelf phase 2

The allogeneic CAR-T cell therapy space is set for its biggest test yet. After ironing out the protocol with the FDA, Allogene Therapeutics has kicked off the first phase 2 clinical trial of an off-the-shelf candidate, setting it up to show how its CD19-directed prospect fares in a potentially pivotal study. 

It has taken longer than expected to reach this point. Allogene was held up by a clinical hold late last year and then, after resolving the problem, went on to miss its mid-2022 target for the start of its phase 2  trial in large B-cell lymphoma (LBCL), a type of non-Hodgkin lymphoma (NHL). Even so, it appears that Allogene has won the race to move an off-the-shelf candidate into phase 2. 

The Allogene clinical trial will study a single dose of ALLO-501A. Allogene has previously posted clinical data that suggests there are benefits to repeat dosing, reporting the conversion of four patients from partial to complete responses last summer after a second infusion of ALLO-501 or ALLO-501A.

In its statement to disclose the start of the phase 2, Allogene said the protocol is “supported by clinical and translational data from [a] phase 1 trial indicating deep responses are achievable with a single dose of ALLO-501A when used with a lymphodepletion regimen that includes an optimized dose of [anti-CD52 monoclonal antibody] ALLO-647.” 

Participants in the phase 2 trial will receive 90 mg of ALLO-647. At that dose, 86% of participants had (PDF) a grade 3 or worse treatment emergent adverse event in earlier NHL trials, compared to 71% of subjects on the 60-mg dose. The higher dose was associated with a much higher rate of bacterial of viral infection, 72% versus 29% at 60 mg, and of grade 3 or worse infection, 28% versus 14%.

However, with the studies also linking higher ALLO-647 exposure to deeper, longer lymphodepletion and higher IL-15 levels, Allogene has chosen the 90-mg dose. The biotech is running a separate, potentially registrational trial of ALLO-647, in which around 70 LBCL patients will receive a single dose of ALLO-501A plus one of two lymphodepletion regimens with and without the anti-CD52 antibody.