Bifunctional Immunotherapy M7824 in Cancer

Mer­ck, a sci­ence and tech­nol­o­gy com­pa­ny, announced that the Euro­pean Med­i­cines Agency (EMA) has grant­ed orphan drug des­ig­na­tion (ODD) to M7824, for the treat­ment of bil­iary tract can­cer (BTC). The EMA ODD fol­lows the Food and Drug Admin­is­tra­tion (FDA) also grant­i­ng orphan drug des­ig­na­tion to M7824 in BTC just weeks ago. M7824 is an inves­ti­ga­tion­al bifunc­tion­al immunother­a­py designed to com­bine co-local­ized block­ing of the trans­form­ing growth factor‑β (TGF‑β) and PD-L1 immune escape mechanisms.

“EMA orphan drug des­ig­na­tion is anoth­er recog­ni­tion of Merck’s deter­mi­na­tion to bring inno­v­a­tive ther­a­pies to peo­ple suf­fer­ing from chal­leng­ing can­cers like bil­iary tract can­cer. This is the sec­ond orphan drug des­ig­na­tion for M7824 in a mat­ter of weeks and Mer­ck is eager to fur­ther explore the poten­tial of this new class of immunother­a­py to advance out­comes in a num­ber of dif­fi­cult-to-treat tumors.”

Luciano Ros­set­ti, Head of Glob­al Research & Devel­op­ment at the Bio­phar­ma Busi­ness of Merck

BTC is a col­lec­tive term for a group of rare and aggres­sive gas­troin­testi­nal can­cers, includ­ing intra­hep­at­ic cholan­gio­car­ci­no­ma (ICC), extra­hep­at­ic cholan­gio­car­ci­no­ma (ECC), and gall­blad­der car­ci­no­ma (GBC).1 Approx­i­mate­ly 186,000 cas­es of BTC are esti­mat­ed to occur annu­al­ly worldwide.2 Treat­ment options are lim­it­ed and the medi­an sur­vival rate in the advanced set­ting is less than one year; objec­tive tumor response with com­mon­ly used chemother­a­py is typ­i­cal­ly less than 10% with short dura­tion of response.1,3,5

EMA orphan des­ig­na­tion is designed to encour­age the devel­op­ment of new treat­ments for life-threat­en­ing or chron­i­cal­ly debil­i­tat­ing con­di­tions that are rare (affect­ing not more than five in 10,000 peo­ple in the Euro­pean Union). Med­i­cines that meet the EMA’s orphan des­ig­na­tion cri­te­ria qual­i­fy for a num­ber of incen­tives to help sup­port advancement.

The first clin­i­cal data for M7824 in BTC, pre­sent­ed at the Euro­pean Soci­ety of Med­ical Oncol­o­gy (ESMO) con­gress in Octo­ber, demon­strat­ed clin­i­cal activ­i­ty in Asian patients who had pro­gressed after plat­inum-based first-line treat­ment. The over­all response rate (ORR) among the total of 30 patients was 20%, as assessed by an inde­pen­dent review com­mit­tee (IRC), and respons­es were observed across PD-L1 lev­els with a dura­tion of response rang­ing from 8.3 months to 13.9+ months. Grade 3 or high­er treat­ment-relat­ed adverse events (TRAEs) were expe­ri­enced by 10 patients (33.3%) and the most com­mon Grade 3 TRAEs were rash (10%) and lipase increase (10%).

M7824 is an inves­ti­ga­tion­al bifunc­tion­al immunother­a­py that com­bines a TGF‑β trap with the anti-PD-L1 mech­a­nism in one fusion pro­tein. Designed to com­bine co-local­ized block­ing of the two immuno­sup­pres­sive path­ways, M7824 is thought to con­trol tumor growth by poten­tial­ly restor­ing and enhanc­ing anti-tumor respons­es. M7824 is an impor­tant part of a nov­el com­bi­na­tion approach that seeks to har­ness the pow­er of the immune sys­tem and address the tremen­dous­ly com­plex nature of dif­fi­cult-to-treat tumors. To date, more than 670 patients with var­i­ous types of sol­id tumors have been treat­ed across the pro­gram with M7824. In addi­tion to BTC, M7824 is being stud­ied in sol­id tumor indi­ca­tions, includ­ing non-small cell lung can­cer, HPV asso­ci­at­ed tumors and gas­troin­testi­nal can­cers, such as gas­tric can­cer, esophageal squa­mous cell car­ci­no­ma and esophageal adenocarcinoma.