#AACR: Bris­tol-My­ers tunes out sta­t­ic, broad­casts im­pres­sive re­sults for Op­di­vo/Yer­voy lung can­cer com­bo

CHICA­GO — Bris­tol-My­ers Squibb $BMY ran smack dab in­to a high lev­el of pro­fes­sion­al sta­t­ic when it changed up its study de­sign for Check­mate-227, a piv­otal test for Op­di­vo plus Yer­voy in treat­ing new cas­es of non-small cell lung can­cer. But they’ve ar­rived at AACR with da­ta they say spell out a com­pelling case for their PD-1/CT­LA-4 com­bo.

Fouad Namouni

“The da­ta we re­port here are ex­cit­ing,” says Fouad Namouni, the on­col­o­gy de­vel­op­ment chief at Bris­tol-My­ers, “with an im­por­tant lev­el of ac­tiv­i­ty.”

Their drug re­duced the risk of pro­gres­sion or death by 42% with a haz­ard ra­tio of 0.58.

At the one-year mark, Namouni told me in a pre­view of to­day’s re­lease, the pro­gres­sion-free sur­vival rate in the com­bo arm was 43%, com­pared to on­ly 13% in the con­trol arm. And that’s re­gard­less of PD-L1 ex­pres­sion sta­tus and his­tol­ogy, with no changes for squa­mous or non­squa­mous cas­es.

Re­searchers in­volved in the study ripped up the orig­i­nal tri­al de­sign, mesh­ing da­ta to­geth­er and claim­ing a suc­cess against a nov­el goal for pa­tients with a “high tu­mor mu­ta­tion bur­den.” And they went their own way on defin­ing the TMB so that it in­clud­ed close to half of all pa­tients in the pop­u­la­tion, rather than the more min­i­mal sub­group tracked by the test mak­er Foun­da­tion Med­i­cine, which us­es a bar that is set twice as high to clas­si­fy pa­tients.

Clear­ly, Namouni says, this marks a big ad­vance for pa­tients — to say noth­ing about their in­tense ri­val­ry with Mer­ck. And he adds that it makes sense.

“A high tu­mor mu­ta­tion bur­den is a sur­ro­gate for neo-anti­gens,” he adds, which makes the tu­mor more vis­i­ble to the im­mune sys­tem, and in turn makes it more like­ly to be re­spon­sive to a PD-1/L1 check­point.

Their work here, says Namouni, in­volves deep­en­ing the field’s un­der­stand­ing of the bi­ol­o­gy of lung can­cer. 

They’ve al­so got ev­i­dence to back up their po­si­tion that 10 mu­ta­tions/megabase is the right in­flec­tion point, rather than mov­ing the scale up even as high as 15. The Foun­da­tion test sets the mark at 20.

For some ri­vals, that kind of as­ser­tion looks like a boast that can’t be proven at this ear­ly stage of the game. But in a chat with As­traZeneca’s David Berman, their chief of I/O pro­grams, he agreed that their own work backed up the stan­dard used by Bris­tol-My­ers — not­ing that in lung can­cer specif­i­cal­ly 10 mu­ta­tions/megabase marked the right cut­off for the as­say on high TMB. Every can­cer type is dif­fer­ent, he adds, and they’ve been care­ful­ly study­ing this them­selves in their work on dur­val­um­ab in lung can­cer.

There are oth­er prob­lems that are pre­sent­ed by us­ing the test, though. One is that it cur­rent­ly takes about 2 weeks to get back re­sults on the tu­mor mu­ta­tion bur­den, and some crit­ics say pa­tients and doc­tors may not want to de­lay ther­a­py to run the test. But Bris­tol-My­ers’ Namouni says that that is with­in the usu­al con­sul­ta­tion time it takes to de­cide on ther­a­py — adding that what takes 2 weeks now could be quick­ly sliced back to a cou­ple of days with the prop­er fo­cus.

Bris­tol-My­ers’ ap­proach may con­tin­ue to raise hack­les among some ob­servers — but this is a high­ly re­spect­ed R&D or­ga­ni­za­tion that is de­ter­mined to re­main a leader in lung can­cer, come what may or might at Mer­ck or any of its oth­er ri­vals.

Namouni says they’ve been in con­ver­sa­tions with reg­u­la­to­ry groups about the da­ta, but he isn’t of­fer­ing any time­lines on fil­ings. 

John Hood [file photo]

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On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

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