WASH­ING­TON, DC — The Can­cer Re­search In­sti­tute has been do­ing the math on the PD-1/L1 check­point pipeline, and you might not be­lieve what we’re see­ing now in terms of clin­i­cal re­search pro­grams.

Samir Khleif

In a dis­cus­sion here at the So­ci­ety for Im­munother­a­py of Can­cer meet­ing, Samir Khleif, an im­muno-on­col­o­gist and SITC board mem­ber, laid out the num­bers from the CRI.

With 5 check­points on the mar­ket, there are now 164 dif­fer­ent check­point ther­a­pies be­ing stud­ied from the pre­clin­i­cal through late-stage phase. There are three more right now in Phase III — REGN-2810 from Sanofi/Re­gen­eron, PDR001 from No­var­tis and INC­SHR-1210 from In­cyte/Jiang­su Hen­grui — and 9 in Phase II.

CRI counts 1,502 clin­i­cal tri­als un­der­way in­volv­ing a PD-1/L1, with 1,105 com­bo stud­ies in the pipeline. Quite a few of those tri­als might well pay off, Khleif not­ed, but here’s the prob­lem:

“We are not on the right path,” Khleif tells me. “Cur­rent­ly there are a lot of com­bi­na­tion clin­i­cal tri­als and some of those tri­als are not based on sci­ence.”

Log­ic may lead you to be­lieve that PD-1/L1 com­bined with just about any­thing else will work bet­ter, he says. But that isn’t al­ways so. You might think that a check­point and OX40 would work to­geth­er, he used by way of ex­am­ple, by elim­i­nat­ing the sup­pres­sive en­vi­ron­ment in the tu­mor. But the com­bi­na­tion ac­tu­al­ly in­hibits im­mune re­sponse, he says, which has been shown in an­i­mal stud­ies.

The gold rush on I/O, though, is caus­ing bio­phar­mas and re­searchers to rush in­to tri­als where they haven’t done the sci­ence to check and see if they have a rea­son­able chance of suc­cess.

In the mean­time, he adds, it’s be­come hard­er and hard­er to find can­cer pa­tients for these stud­ies. “We’re go­ing to have prob­lems re­cruit­ing pa­tients any way,” Khleif says, mak­ing it all that more im­por­tant to make sure that pro­grams aren’t rushed in­to the clin­ic.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.