ASH 2025 – Gilead spills the beans on “fast” Car-T

While several cell therapy players are betting on improved processes to speed the manufacturing of Car-T therapies it’s long been clear that the time saved is relatively insignificant compared with long waits patients still have to endure before receiving their treatment.

Gilead effectively admitted as much during ASH, revealing that a phase 1 study of its fast-manufactured contender KITE-753 had to bridge a third of the patients enrolled to keep their disease from progressing while they awaited a manufacturing slot. But the company proposed a separate advantage for KITE-753: fast manufacturing results in a better product, with younger and fitter T cells.

The company has the advantage of being able to compare directly a Car-T product manufactured using “rapid” versus traditional manufacturing: KITE-363 and KITE-753 are structurally identical products that generate bicystronic anti-CD19 and anti-CD20 Car-T constructs, but the former uses a traditional cell therapy manufacturing process.

First KITE-753 results

The ASH presentation over the weekend related to the first human data generated with KITE-753. On the face of it the results were typically impressive: an 80% response rate among 20 Car-naive B-cell lymphoma patients at 21 August data cutoff, including 86% among 14 given dose level 3. For dose level 3 the complete response rate was 71%, rising to 79% at a later cutoff of 24 October.

But, while such numbers broadly mirrored results earlier presented with KITE-363, the real benefit emerges in the fact that they were achieved at one tenth the dose of KITE-363: “dose level 3” was 200,000 Car-T cells for KITE-753, versus 2 million cells for the traditionally manufactured product.

Presenting the ASH data Dr Saurabh Dahiya, of Stanford University School of Medicine, said the rapid manufacturing process used for KITE-753 preserved naive and stem cell memory T cells. This results in relatively fit cells that are less prone to exhaustion than is the case for traditional production.

The suggestion is that KITE-753 could have more durable efficacy than KITE-363, with less toxicity. And the ASH data appeared to back up the second point, with no severe CRS or ICANS at all, and only two patients developing ICANS at any grade; that’s meaningfully better than the numbers KITE-363 put up at the European Hematology Association conference earlier this year.

Comparison of dose level 3 for traditional vs rapid-manufactured anti-CD19 x CD20 Car-T therapy

Note: ICANS=immune effector cell-associated neurotoxicity syndrome. Source: EHA and ASH.

Given such advantages it might seem curious that Gilead hasn’t bet firmly on KITE-753, merely stating that the projects are efficacious and well tolerated, and that the data support the development of both of them. 

Still, KITE-753 is quietly being prioritised. While KITE-363 is being taken forward in immunology, no pivotal trial plans for it in haematological cancer have been disclosed; in contrast, KITE-753 is to enter a “pivotal” phase 2 study in third-line B-cell lymphoma early next year, and at ASH Gilead revealed plans for a second-line, randomised, controlled phase 3 trial.

Other companies active in fast Car-T manufacturing include Novartis, Bristol Myers Squibb and AstraZeneca (via its Gracell acquisition). Nevertheless, while speed of production has long been the claim, early data on Novartis’s rapcabtagene autoleucel revealed some patients having to wait as long as six months to receive therapy, resulting in many having to be bridged with chemo.

This problem isn’t going to be solved any time soon: 33% of patients in Gilead’s KITE-753 trial, and 37% on dose level 3, had to be bridged while awaiting therapy, in this case not with chemo but with steroids and/or radiotherapy.