Pfiz­er, Mer­ck KGaA say their PD-L1 Baven­cio al­so flunked PhI­II in the all-im­por­tant lung can­cer field

Play­ing catch-up in the crowd­ed PD-1/L1 field in can­cer R&D is prov­ing par­tic­u­lar­ly tough for Mer­ck KGaA and Pfiz­er $PFE.

The part­ners re­port­ed this morn­ing that their Phase III lung can­cer study JAVELIN Lung 200 failed the pri­ma­ry end­point for over­all sur­vival com­par­ing Baven­cio (the PD-L1 avelum­ab) against do­c­etax­el in sec­ond-line lung can­cer, a ma­jor field for all the play­ers in this par­tic­u­lar field.

Re­searchers swift­ly fin­gered the crossover of pa­tients to oth­er avail­able check­points as a like­ly rea­son for the flop — rais­ing a threat that may well arise for every­one test­ing check­points in the all-im­por­tant group of lung can­cer pa­tients.

De­tails are scant as the da­ta will be pre­sent­ed at an up­com­ing con­fer­ence, but the part­ners made sure to pro­vide an ex­pla­na­tion:

While the tri­al did not meet its pre­spec­i­fied end­point of im­prov­ing over­all sur­vival (OS) in pa­tients with pro­grammed death lig­and-1-pos­i­tive (PD-L1+) (1% or high­er) tu­mors (HR: 0.90 [96% CI: 0.72–1.12], p-val­ue 0.1627, one-sided), the pro­por­tion of pa­tients in the chemother­a­py arm cross­ing over to im­mune check­point in­hibitors out­side the study was high­er than pre­vi­ous­ly re­port­ed in post-plat­inum im­munother­a­py clin­i­cal tri­als, and this may have con­found­ed this tri­al out­come.

Re­searchers al­so point­ed to im­prove­ments in OS in a sub-group with mod­er­ate-to-high and high PD-L1+ ex­pres­sion, as well as lack of new safe­ty con­cerns, as pos­i­tive signs. But they face some tough com­peti­tors in lung can­cer, where Mer­ck has been mak­ing head­way with Keytru­da as Bris­tol-My­ers Squibb and As­traZeneca fight to gain ground. And the com­pa­nies got some kick­back from Ever­core ISI’s Uber Raf­fat: “The news to­day on Pfiz­er’s 2L lung fail­ure marks the first time we can start to say that PFE may have un­der­per­formed.”

Raf­fat al­so ques­tioned if crossovers could re­al­ly ex­plain the set­back, as Mer­ck has re­port­ed suc­cess be­fore in stud­ies with a 15% crossover rate.

The two big part­ners won an ap­proval to use their PD-L1 drug against Merkel cell car­ci­no­ma, but they’re find­ing it tough ex­pand­ing its use to oth­er can­cers. Just a cou­ple of months ago they al­so re­port­ed that Baven­cio had failed a Phase III study for gas­tric can­cer, putting a crimp in their plans to ramp up sales.

Chris Boshoff

“We are com­mit­ted to un­der­stand­ing the da­ta in the con­text of the sub­pop­u­la­tions and the im­pact of ac­cess to oth­er im­mune check­point in­hibitors,” said Chris Boshoff, a se­nior vice pres­i­dent and head of im­muno-on­col­o­gy at Pfiz­er. “We will con­tin­ue to progress the broad avelum­ab pro­gram, ex­plor­ing var­i­ous in­di­ca­tions.”


With con­tri­bu­tion from John Car­roll.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

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UP­DAT­ED: Pfiz­er hits the brakes on their piv­otal tri­al for a BC­MA/CD3 bis­pe­cif­ic on safe­ty con­cerns while FDA road­block is hold­ing up Duchenne MD PhI­II

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The pharma giant said in a release this morning that they have halted enrollment for their MagnetisMM-3 study after researchers tracked three cases of peripheral neuropathy in the ongoing Phase I. They are now sharing info with the FDA as they explore the red safety flag.

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Stéphane Bancel at the Endpoints #JPM20 breakfast panel in San Francisco, January 2020 (Photo: Jeff Rumans, Endpoints News)

Mod­er­na says Covid-19 vac­cine boost­er in­creased im­mune re­sponse against vari­ants of con­cern

About a month after announcing their variant-specific Covid-19 vaccine boosters showed promising results in mice, Moderna says it now has some human data to back it up.

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CN Bio said the scope of the research performed by the FDA’s Center for Drug Evaluation and Research has expanded to include the exploration of the company’s lung-on-a-chip system to help with the agency’s evaluation of inhaled drugs, in addition to the agency’s work on its liver model.

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A recent update to the FDA’s running tally of how it’s meeting its user fee-related performance goals during the pandemic shows an agency that is not out of the woods yet.

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Cynthia Butitta (L) and Joe Jimenez

Is that an­oth­er IPO in the mak­ing? Ex-No­var­tis CEO Joe Jimenez and a lead Kite play­er take up new posts at an off-the-shelf ri­val to 2 pi­o­neer­ing drugs

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Joe Wiley, Amryt CEO

A biotech with a yen for pricey rare dis­ease drugs — and bar­gain base­ment shop­ping — adopts an­oth­er or­phan in lat­est M&A pact

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Ngozi Okonjo-Iweala, Director general of WTO (AP Photo/Keystone/Alessandro Della Bella)

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