Checkpoint combos for cancer are all the rage as trial sponsors line up hundreds of new studies — report

Num­ber of Anti-PD-1/PD-L1 MAb com­bi­na­tion stud­ies 2015 vs. 2017
Full Re­port: Eval­u­ate Ltd. May 2017

Over the last few months it hasn’t been un­usual to see new com­bi­na­tion stud­ies being an­nounced on a daily basis, match­ing one of the 5 ap­proved PD-(L)1 check­point drugs with an­other can­cer ther­apy. Some morn­ings they come in pairs.

It’s not hard to see why. The check­points typ­i­cally work as a monother­apy — though there have been some nasty set­backs over the past 6 months. And some of the big play­ers are happy to con­tribute their drug to stud­ies spon­sored by oth­ers look­ing to ad­vance a pilot Phase I/II ex­ploratory study. There are also re­cent ex­am­ples of some big tie-ups be­tween Merck (Keytruda) and Bris­tol-Myers Squibb (Op­divo) check­points with In­cyte in Phase III.

In­cyte has its own PD-1 in the clinic as it lines up these ag­nos­tic late-stage tri­als to po­si­tion its lead­ing IDO1 drug.

Now EP Van­tage has tal­lied the whole score on these combo tri­als, not co­in­ci­den­tally just ahead of ASCO, and found a stun­ning 765 com­bi­na­tion stud­ies listed on clin­i­cal­tri­als.gov. Keytruda leads the pack, with 268 — up from 70 just 18 months ago. For Bris­tol-Myers it’s 242, more than three times the num­ber EP Van­tage’s ed­i­to­r­ial team found in 2015.

Any­one even mod­er­ately in­ter­ested in this field will want to check it out di­rectly. There’s a lot of de­tail on what’s now in the clinic.

Don’t ex­pect the ris­ing trend lines to start to plateau any­time soon, ei­ther, as Pfizer/Merck KGaA (Baven­cio) and As­traZeneca (Imfinzi) start to gain trac­tion on the combo front. Roche al­ready emerged as the num­ber three player in the field with Tecen­triq, though its re­cent Phase III fail­ure for its check­point may chill other would-be part­ners.

Mean­while, new check­point play­ers like BeiGene and Lilly are mov­ing along, the re­port notes, while No­var­tis has been ad­vanc­ing its own in-house check­point pro­grams. The sec­ond wave of PD-(L)1 ther­a­pies will be large.

One of the key next steps in this field is in As­traZeneca’s hands. It has a combo of Imfinzi with an in-house CTLA-4 check­point dubbed treme­li­mumab in the MYS­TIC study that will read out soon for lung can­cer. An­a­lysts are wait­ing ea­gerly to see if it can beat out the com­pe­ti­tion, or get side­lined by some well-known tox­i­c­ity con­cerns.

One thing is ab­solutely cer­tain. Bris­tol-Myers Squibb started as the dom­i­nant player in PD-(L)1, then got checked by a surg­ing Merck when it made the wrong clin­i­cal move on non-small cell lung can­cer. As­traZeneca, the last of the big 5 to land an ap­proval, just days ago stunned vir­tu­ally every­one with pos­i­tive Phase III data for Imfinzi in un­re­sectable lung can­cer, pro­vid­ing early dom­i­nance in a sig­nif­i­cant niche mar­ket.

The Big Pharma’s stock soared as an­a­lysts began to cal­cu­late what that is worth.

Just at a time when check­points should start get­ting more pre­dictable, the field seems to be ripe for fresh sur­prises of all kinds. And that will con­tinue to at­tract fresh waves of com­bi­na­tion stud­ies tack­ling all kinds of can­cers.

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