Mer­ck took a dom­i­nant po­si­tion in front­line lung can­cer with the ap­proval of a com­bi­na­tion of Keytru­da and chemo. And it isn’t just wait­ing around to see if any com­bi­na­tion of a PD-(L)1 with a CT­LA4 can come along and knock it off its mar­ket-lead­ing perch.

The phar­ma gi­ant has launched a Phase III study com­bin­ing its check­point star with the Bris­tol-My­ers drug. Re­searchers are re­cruit­ing 548 pa­tients at sites around the world, ac­cord­ing to the list­ing at clin­i­cal­tri­als.gov.

The ju­ry is still def­i­nite­ly out on how a PD-(L)1/CT­LA-4 com­bo will work. Yer­voy and its class has been ef­fec­tive in im­prov­ing sur­vival rates, but they’re al­so as­so­ci­at­ed with sig­nif­i­cant tox­i­c­i­ty, which makes their use prob­lem­at­ic.

Mer­ck al­so has its own CT­LA-4 (MK-1308), which it is com­bin­ing with Keytru­da. So why add Yer­voy to the mix?

The sim­plest ex­pla­na­tion may be that Mer­ck, which has hun­dreds of com­bo stud­ies un­der­way, is try­ing every­thing. It’s al­so been spurred on by Bern­stein’s Tim An­der­son.

Since 2016, we have ar­gued it would be wise for MRK to run com­bi­na­tion tri­als of Keytru­da+Yer­voy tri­al in 1L lung can­cer.  Even though MRK does not own Yer­voy, it could still eas­i­ly de­sign a study like this, and it would be a hedge against the pos­si­bil­i­ty that AZN’s MYS­TIC and BMY’s Check­mate-227 show that CT­LA4+PDx com­bi­na­tion ther­a­py is vi­able (its vi­a­bil­i­ty re­mains un­clear at the mo­ment).

MYS­TIC, of course, has proven to be some­thing of an em­bar­rass­ment to As­traZeneca so far, with dur­val­um­ab and treme­li­mum­ab miss­ing the first goal on pro­gres­sion-free sur­vival. They’re still shoot­ing for over­all sur­vival, though, and aren’t com­plete­ly count­ed out in a field that rou­tine­ly pro­vides ex­tra­or­di­nary sur­pris­es.

An­der­son has urged Mer­ck to “go big or go home” on this front. I have no idea what Mer­ck, which went big on Keytru­da sev­er­al years ago, thought of that. But An­der­son has some in­flu­ence here and is not to be ig­nored.

The tri­al will on­ly en­roll high PDL1 ex­pressers (>50%), and bold­ly, it will com­pare this com­bi­na­tion to Keytru­da monother­a­py (which has be­come stan­dard of care any­way; re­call that MYS­TIC and ‘227 don’t have a PDx as a com­para­tor, but on­ly con­ven­tion­al chemother­a­py). The pri­ma­ry end­points are PFS and OS, but re­sults won’t be in hand un­til 2022 per clin­i­cal­tri­als.gov (link); this time­line is ar­guably con­ser­v­a­tive.

Bris­tol-My­ers and Cy­tomX, mean­while, are work­ing on a new CT­LA-4 that they hope will prove just as ef­fi­ca­cious or more while sig­nif­i­cant­ly less tox­ic.

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.

Digital therapeutics company Better Therapeutics announced on Thursday that it’s cutting 35% of its staff as it awaits FDA clearance for its first product.

The company, which launched eight years ago, is one of a growing group of companies seeking a digital alternative to traditional medicine. The space saw a record $7.5 billion in investments in 2021, according to Chris Dokomajilar at DealForma, with uses spanning ADHD, PTSD and other indications. However, private insurers have been slow to hop on board.