CHICA­GO — Mer­ck came to AS­CO as the dom­i­nant in­dus­try play­er in front­line lung can­cer. It’s go­ing to leave AS­CO with that rep in­tact — at the ex­pense of its heavy­weight ri­vals in the field still play­ing catch-up.

Roy Baynes

In two key stud­ies out this morn­ing, the phar­ma gi­ant spelled out pos­i­tive, crit­i­cal­ly im­por­tant da­ta un­der­scor­ing Keytru­da’s abil­i­ty to fight a broad seg­ment of the cas­es in the first-line lung can­cer field as a monother­a­py, with the Keytru­da/chemo com­bo the best op­tion (so far) in front­line squa­mous cas­es, where Roche tried — and large­ly failed — to el­bow ahead this week­end.

“If you think of the whole front­line lung can­cer field (ex­cept for EGFR and ALK mu­ta­tion cas­es),” says Mer­ck head of glob­al clin­i­cal de­vel­op­ment Roy Baynes, “for pret­ty much every­body there is a Keytru­da-based ther­a­py that makes sense for those pa­tients. It would be fair to say, all things be­ing equal, the chemo com­bi­na­tion is a very rea­son­able first-line op­tion.”

But not every­one is go­ing to be able to take the chemo com­bo, in­clud­ing pa­tients with high co-mor­bidi­ties. 

“Giv­en the sit­u­a­tion of all things be­ing equal, the chemo com­bo would be a pre­ferred ther­a­py,” says Baynes. “And if there are cir­cum­stances where chemo is not a pre­ferred ther­a­py, monother­a­py is a rea­son­able op­tion.”

In its monother­a­py study dubbed Keynote-042, pa­tients in the Keytru­da arm hit a me­di­an over­all sur­vival rate of 20 months, a clear­ly promis­ing out­come com­pared to 12.2 months for chemo-so­lo pa­tients with a PD-L1 tu­mor pro­por­tion score (TPS) of ≥50 per­cent. In pa­tients with a TPS of less than 20%, the OS rate was re­duced to 17.7 vs 13 months, and 16.7 vs 12.1 months for the over­all study pop­u­la­tion of pa­tients with a TPS of ≥1%.

The ‘042 study was the longer take of an ear­li­er, faster tri­al num­bered ‘024. And Mer­ck views it as a more thor­ough con­fir­ma­tion of what it saw in that quick take.  

Then there’s Keynote-407, a com­bi­na­tion of Keytru­da and chemo for front­line squa­mous NSCLC  which had es­sen­tial­ly the same de­sign as Roche’s IM­pow­er131, with Tecen­triq. Mer­ck’s team post­ed an im­pres­sive 36% re­duc­tion in the risk of death, a haz­ard ra­tio that won’t es­cape the at­ten­tion of spe­cial­ists. The Keytru­da com­bi­na­tion hit a me­di­an OS of 15.9 months com­pared to 11.3 months in the chemother­a­py-alone group. The me­di­an PFS was 6.4 months for the Keytru­da com­bi­na­tion com­pared with 4.8 months for chemother­a­py alone. 

And at the sec­ond in­ter­im read­out, the ORR was 57.9% for the com­bo com­pared to 38.4% for the chemother­a­py group. 

Roche has yet to see an OS ad­van­tage, but the PFS was close at 6.3 months for the Roche check­point vs 5.6 months for the con­trol — just a 3 week ad­van­tage. As al­ways when you com­pare da­ta on drugs that were not in a head-to-head tri­al, it’s prob­lem­at­ic to as­sess ri­val ther­a­pies. But with­out com­pet­i­tive OS re­sults, Roche is left with a small ad­van­tage in PFS that won’t com­pare well for an­a­lysts cov­er­ing the area.

The new da­ta sets will al­so in­evitably draw com­par­isons with Bris­tol-My­ers Squibb’s work with Op­di­vo. Bris­tol-My­ers has faced some stiff crit­i­cism for its set­backs as well as its tri­al de­signed in lung can­cer, where they’ve been a con­sis­tent run­ner up to Mer­ck.

The re­sults build on the re­cent­ly re­leased da­ta from Keynote-189 for non­squa­mous non-small cell lung can­cer, where re­searchers say that their com­bo of Keytru­da and chemo clear­ly beat out chemo alone on over­all sur­vival, though the fi­nal OS rate for the com­bi­na­tion has not yet been reached.

For Mer­ck, it’s an­oth­er chance to cel­e­brate pos­i­tive out­comes as ri­vals strug­gle to make their case for their drugs.

“As we look at the lung can­cer are­na,” Baynes adds, “we com­plet­ed 5 ran­dom­ized, con­trolled tri­als, with sur­vival ben­e­fits in all 5. It’s quite re­mark­able.”

Not every­one is pro­vid­ing Mer­ck with a stand­ing ova­tion, though. Some prac­ti­tion­ers in the field feel that those groups with a low­er TPS score on PD-L1 are def­i­nite­ly not get­ting a tremen­dous amount of help from Keytru­da. Here’s a note from lung can­cer ex­pert Jack West — a tho­racic on­col­o­gist at the Swedish Can­cer In­sti­tute at Swedish Med­ical Cen­ter — about my sto­ry:

Though I com­plete­ly agree that re­sults over­all are im­pres­sive and that Mer­ck is more or less run­ning the ta­ble with pem­bro in ad­vanced NSCLC, I need to high­light that the re­sults are not as fa­vor­able as your lan­guage would syggest for the pa­tients with low PD-L1 on KEYNOTE-042. The num­bers you use for pa­tients with low­er tu­mor PD-L1 ex­pres­sion in­clude the pa­tients with high PD-L1, who prop up the re­sults for the en­tire tri­al. When the re­sults of the 042 tri­al are looked at for pa­tients with PD-L1 1-49%, there is no ef­fi­ca­cy ad­van­tage for pem­bro. This doesn’t mean that on­col­o­gists and pa­tients won’t fa­vor it for com­pa­ra­ble ef­fi­ca­cy and more fa­vor­able tol­er­a­bil­i­ty than chemo, but it’s im­por­tant to clar­i­fy that the num­bers you’re pre­sent­ing for the “PD-L1 less than 20%” are ac­tu­al­ly not the num­bers for that sub­set alone but the num­bers for that sub­set com­bined with the larg­er num­ber of pa­tients with high­er tu­mor PD-L1 ex­pres­sion. The re­sults are pooled and mere­ly don’t “de-se­lect” the low PD-L1 group when they present “PD-L1 <50%” or “PD-L1 < 20%”, but they al­ways in­clude the pa­tients with high­er PD-L1 who are prop­ping up the tri­al over­all. And this is the sub­group for whomp pem­bro alone has been the stan­dard of care for more than 18 months, for whom we’d al­ready con­sid­er chemo alone an es­tab­lished in­fe­ri­or ap­proach in the US and wouldn’t en­roll on KN-042 these days.

Mer­ck has been pour­ing bil­lions of dol­lars in­to its Keytru­da pipeline, and the in­vest­ment has paid off hand­some­ly with a block­buster fran­chise and a col­lec­tion of more than 750 tri­als — an ex­plo­sion of clin­i­cal re­search. Five years ago, says Baynes, Mer­ck was at AS­CO with one pre­sen­ta­tion. For AS­CO 2018, it’s pre­sent­ing 140.

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.