On CAR-T’s Edge, Seattle Researchers Plot to Bypass Novartis Therapy

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in PLAT-02 then pull them out and re-assign them into three different arms of PLAT-03, based on the underlying warning signs of a potential relapse.

One NIH reviewer last year warned the Seattle Children’s team about the “Roy Rogers effect.” He was mixing up his homespun cowboy entertainers, and actually meant the Will Rogers effect, which is this: by taking certain members from one group and putting them in another, you can make both groups look better. (It’s based on Will Rogers’s quip that the Dust Bowl migration from Oklahoma to California in the 1930s raised the IQ of both states.)

“Think about how to ethically report that information,” said Dean Lee, director of cellular therapy at The Ohio State University Comprehensive Cancer Center.

Another concern raised by NIH reviewers was that kids who make it to PLAT-02 have been through so much—think of Greta Oberdorfer’s chemotherapy, bone marrow transplant, and organ failures, not to mention the underlying cancer, all before her second birthday. Would layering them with more complex cell therapies produce too much statistical complexity?

One year after hearing those concerns, the Children’s team has not changed the trial design. Two more trials, PLAT-04 and PLAT-05, are also underway or nearly so, to attack leukemia that has relapsed with a different protein, CD22, on its surface. In total the PLAT series are designed to give the Seattle Children’s researchers a roadmap for turning CAR-T into a therapy that can be used before the last-ditch scenario it’s now approved for.

There are major obstacles. Seattle Children’s has funding for the new PLAT trials, but if success points to a bigger study, it’s not clear who would fund it. Juno is in negotiation with Children’s for right of first refusal, but it’s not signed and sealed, according to Jensen. (Juno officials did not comment.)

And while the FDA approved Kymriah based on data showing one month of remission, it will take more to convince regulators that a toolbox of T cell therapies can potentially replace bone marrow transplants. Jensen admits that confidence about cures will take a long time. “Leukemia can sit dormant for years,” he says. “We use a benchmark in the field of five years.”

But the effort is well worth it, one NIH reviewer at the meeting said last year, calling it “an important study.” University of Chicago bioethicist Laurie Zoloth often has pointed questions for the companies and academics whose work she reviews. More prominent than her critique of the Seattle Children’s plan last year, however, was her praise: “The fact that you’re seeking a better therapy shows your dedication to this group of patients.”

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