The FDA’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee will meet this Thurs­day to dis­cuss whether pro­posed stud­ies would sup­port an ac­cel­er­at­ed ap­proval for GSK’s Jem­per­li in rec­tal can­cer — de­spite ini­tial con­cerns about the tri­al plans.

GSK’s PD-1 block­er Jem­per­li, al­so known as dostar­limab, was first ap­proved back in 2021 for a spe­cif­ic sub­set of re­cur­rent or ad­vanced en­dome­tri­al can­cer pa­tients who have a ge­net­ic fea­ture called dMMR, or de­fi­cient mis­match re­pair. The la­bel was ex­pand­ed months lat­er to in­clude all adults with dMMR re­cur­rent or ad­vanced sol­id tu­mors who have pro­gressed or stag­nat­ed on ear­li­er ther­a­py.

Now, GSK is look­ing to reach “lo­cal­ly ad­vanced, treat­ment-naïve mis­match re­pair de­fi­cien­cy/mi­crosatel­lite in­sta­bil­i­ty-high rec­tal can­cer” — and it’s hop­ing the re­sults from two pro­posed sin­gle-arm tri­als will sup­port an ac­cel­er­at­ed ap­proval. One of those tri­als would en­roll 30 pa­tients in a sin­gle-cen­ter tri­al, and the oth­er would en­roll 100 pa­tients across mul­ti­ple tri­al sites.

ODAC is con­ven­ing on Thurs­day to dis­cuss the pro­posed tri­als, and on Tues­day, reg­u­la­tors re­leased brief­ing doc­u­ments spelling out their con­cerns.

Af­ter dis­cussing the plans, ad­comm mem­bers will vote on the ques­tion: “Will the da­ta from the pro­posed sin­gle arm tri­als en­rolling a to­tal of 130 pa­tients be suf­fi­cient to char­ac­ter­ize the ben­e­fits and risks of dostar­limab in the cu­ra­tive in­tent set­ting for pa­tients with dMMR/MSI-H LARC?”

While GSK has ar­gued that the rar­i­ty of the dis­ease would make ran­dom­ized tri­als in the spe­cif­ic sub­set of lo­cal­ly ad­vanced rec­tal can­cer “in­fea­si­ble,” the FDA not­ed in its brief­ing doc­u­ments that the agency has “gen­er­al­ly re­quired ran­dom­ized tri­als to sup­port the safe­ty and ef­fi­ca­cy eval­u­a­tion of dostar­limab.”

The FDA al­so in­clud­ed a brief analy­sis of GSK’s pro­posed end­points for the tri­als, in­clud­ing an in­ter­me­di­ate end­point of clin­i­cal com­plete re­sponse rate (cCR) at 12 months.

How­ev­er, FDA not­ed:

The use of cCR in LARC clin­i­cal de­ci­sion-mak­ing is based on small, most­ly ret­ro­spec­tive, un­con­trolled stud­ies that vary in de­sign and oth­er im­por­tant fac­tors (e.g., chemother­a­py reg­i­men used, ra­dio­ther­a­py pro­to­col, mon­i­tor­ing pro­to­col for as­sess­ment of cCR, method of as­sess­ing clin­i­cal cCR, pa­tient se­lec­tion, etc.,) thus lim­it­ing the in­ter­pretabil­i­ty of find­ings.

Reg­u­la­tors con­tin­ued that while pre­lim­i­nary da­ta showed a cCR rate of 100% at one site, “it is un­clear whether these re­sults will be replic­a­ble across more sites,” not­ing the pos­si­bil­i­ty of vari­abil­i­ty in lo­cal ex­per­tise. Al­so from the doc­u­ments:

GSK pro­pos­es to use cCR36 as as­sessed by the in­ves­ti­ga­tor and event-free sur­vival at 36 months as as­sessed by ICR to ver­i­fy the clin­i­cal ben­e­fit of dostar­limab if ac­cel­er­at­ed ap­proval is grant­ed. Time-to-event end­points are chal­leng­ing to in­ter­pret in sin­gle-arm tri­als, and, giv­en the het­ero­gene­ity of the da­ta de­scrib­ing re­lapse in LARC, com­par­i­son to his­tor­i­cal con­trol may be chal­leng­ing.

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.