Skep­tics pounce af­ter Bris­tol-My­ers scores an ear­ly hit on Op­di­vo-Yer­voy com­bo for lung can­cer

Bris­tol-My­ers Squibb’s close­ly watched study dubbed Check­mate-227 hit ear­ly, with re­searchers tout­ing a suc­cess for their com­bi­na­tion of Op­di­vo and Yer­voy in treat­ing front­line non-small cell lung can­cer cas­es.

Gio­van­ni Caforio

In a state­ment the com­pa­ny $BMY says that re­searchers tracked a “high­ly” sig­nif­i­cant pro­gres­sion-free sur­vival rate for pa­tients with a high tu­mor mu­ta­tion bur­den (TMB), re­gard­less of PD-L1 ex­pres­sion. Their com­bi­na­tion was com­pared with chemo in the study, which is still track­ing for over­all sur­vival re­sults.

That’s a sig­nif­i­cant group, an­a­lysts note, point­ing to Bris­tol-My­ers’ pro­jec­tion that the TMB crowd ac­counts for 45% of all front­line pa­tients. Bris­tol-My­ers re­designed the study to go af­ter the bio­mark­er af­ter stum­bling on a piv­otal tri­al that in­volved a pa­tient pop­u­la­tion that was not so nar­row­ly de­fined. All the de­vel­op­ers are shift­ing to a bio­mark­er fo­cus as they duke it out for spe­cif­ic slices of a mega block­buster-sized mar­ket.

Skep­tics, though, be­gan to re­tal­i­ate ear­ly, and af­ter a sharp jump ear­ly in the day, shares are trad­ing down 3% as crit­ics won­der if Bris­tol-My­ers can fol­low through with con­vinc­ing da­ta. We asked lung can­cer ex­pert Jack West for his take, which you can see here, ques­tion­ing the way the bio­mark­er was han­dled and not­ing that prac­ti­tion­ers will need to see more be­fore chang­ing the way they treat pa­tients.

Hus­tling along in search of pos­i­tive da­ta, Bris­tol-My­ers es­sen­tial­ly in­te­grat­ed two par­al­lel stud­ies in­volv­ing more than 1,700 pa­tients. And R&D chief Tom Lynch told an­a­lysts this morn­ing that there’s more work to be done on TMB-de­fined stud­ies, with up­com­ing da­ta read­outs on gas­tric, lung and head and neck can­cers.

Some an­a­lysts had been won­der­ing if Bris­tol-My­ers might just call a suc­cess to­day, with its Q4 re­port com­ing up. Past mishaps for  Op­di­vo in the all-im­por­tant NSCLC group cost it big time as Mer­ck surged ahead with a com­bi­na­tion of Keytru­da and chemo.

Just a few days ago Sea­mus Fer­nan­dez at Leerink not­ed:

While suc­cess at the OS in­ter­im rep­re­sents a very high bar, this would be a huge­ly pos­i­tive sur­prise. We be­lieve a win here would sug­gest that Op­di­vo + Yer­voy could have a crit­i­cal­ly im­por­tant place in the treat­ment of NSCLC.

Bris­tol-My­ers CEO Gio­van­ni Caforio called it a “break­through in can­cer re­search and a mean­ing­ful step for­ward in de­ter­min­ing which first-line lung can­cer pa­tients may ben­e­fit most from the com­bi­na­tion of Op­di­vo and Yer­voy.”

“TMB has emerged as an im­por­tant bio­mark­er for the ac­tiv­i­ty of im­munother­a­py. For the first time, this Phase 3 study shows su­pe­ri­or PFS with first-line com­bi­na­tion im­munother­a­py in a pre­de­fined pop­u­la­tion of NSCLC pa­tients with high TMB,” said Matthew Hell­mann, study in­ves­ti­ga­tor and med­ical on­col­o­gist at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter. “Check­Mate-227 showed that TMB is an im­por­tant, in­de­pen­dent pre­dic­tive bio­mark­er that can iden­ti­fy a pop­u­la­tion of first-line NSCLC pa­tients who may ben­e­fit from the nivolum­ab plus ip­il­i­mum­ab com­bi­na­tion.”

Not every­one was im­pressed by the top-line re­sults, though.

The win here is al­so a plus for Foun­da­tion Med­i­cine $FMI, which pro­vid­ed the test used to pick pa­tients with a high TMB.

As­traZeneca — which ear­li­er record­ed a ma­jor fail for its com­bi­na­tion of its check­point drug Imfinzi and treme­li­mum­ab, an­oth­er PD-1/L1 check­point com­bined with an ex­per­i­men­tal CT­LA-4 drug — failed the first step on PFS with their com­bo. The OS da­ta is due out lat­er in the year.

The im­pli­ca­tions for Bris­tol-My­ers are con­sid­er­able. An ear­ly leader in the field, the R&D team on Op­di­vo have been work­ing fever­ish­ly to get their PD-1 back on track fol­low­ing a key miss in lung can­cer. But a suc­cess here on PD-1/CT­LA-4 will like­ly trig­ger fresh chat­ter of a pos­si­ble takeover bid by Pfiz­er, which has nev­er lost its ap­petite for a mega-merg­er. On the oth­er hand, such a takeover would al­so threat­en one of the most in­no­v­a­tive of the big bio­phar­ma com­pa­nies.

Op­di­vo earned close to $5 bil­lion last year, a 31% in­crease over 2016, mak­ing this their biggest sell­ing fran­chise drug. Eliquis is now their num­ber two ther­a­py, high­light­ing Op­di­vo’s over­sized role in the com­pa­ny’s fu­ture.

 

Brent Saunders [Getty Photos]

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As­traZeneca chal­lenges Roche on front­line SCLC af­ter seiz­ing an in­ter­im win — and Mer­ck may not be far be­hind

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Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Novotech CEO Dr. John Moller

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Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

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