Bristol Myers Squibb (BMY)

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A LAG-3, Opdivo combo from Bristol-Myers offers a proof-of-concept glimpse of limited success

by john carroll — on June 3, 2017 11:57 AM EDT
Updated: June 5, 2017 05:41 AM

chicago — Now that the first wave of PD-(L)1 drugs has splashed out and is get­ting es­tab­lished in the can­cer mar­ket, one of the next steps down the pipeline in­volves match­ing up check­point in­hibitors in new com­bos as the lead­ers in the field pur­sue a fast and fu­ri­ous R&D strat­egy to mar­ket ex­pan­sion. To that end, Bris­tol-Myers Squibb $BMY turned up at ASCO with some in­trigu­ing proof-of-con­cept data that mar­ries their drug Op­divo with a LAG-3 drug, of­fer­ing an early glimpse on how it could work for a par­tic­u­lar cat­e­gory of pa­tient.


Paolo Ascierto
Their combo, BMS-986016, achieved a 12.5% ob­jec­tive re­sponse rate among 55 melanoma pa­tients who had al­ready been on a PD-(L)1 ther­apy. More im­por­tantly, there was sig­nif­i­cant split in re­sponses among pa­tients based on LAG-3 ex­pres­sion, with 20% of the pa­tients with at least 1% of tumor-as­so­ci­ated im­mune cells within the tumor mar­gin achiev­ing an ORR com­pared to 7.1% with less than 1%.

Jef­feries’ Biren Amin con­cluded that the data were un­der­whelm­ing, but an ad­just­ment around LAG-3 ex­pres­sion could en­hance its fu­ture.

Op­divo was the first of the PD-(L)1s to dom­i­nate the mar­ket, but after Bris­tol-Myers’ trial work de­railed on a mis­step in lung can­cer, the big biotech has dou­bled down on on­col­ogy, shak­ing up its R&D group and tack­ling a steadily widen­ing num­ber of stud­ies. This is one step back in the right di­rec­tion.

“As a po­ten­tially syn­er­gis­tic im­mune path­way to PD-1/PD-L1, LAG-3 has emerged as an im­mune check­point re­cep­tor that reg­u­lates T cell func­tion and whose in­hi­bi­tion may in­crease ben­e­fits for pa­tients,” said Paolo Ascierto of the Is­ti­tuto Nazionale Tu­mori Fon­dazione Pas­cale of Naples, Italy. “These re­sults in­di­cate that BMS-986016 in com­bi­na­tion with Op­divo may offer clin­i­cal ben­e­fit, par­tic­u­larly for pa­tients whose tu­mors con­tain im­mune cells that ex­press LAG-3. Fur­ther in­ves­ti­ga­tion is war­ranted to un­der­stand the im­pact of this com­bi­na­tion as well as the util­ity of LAG-3 as an im­mune bio­marker.”
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