Ex­elix­is, Bris­tol-My­ers mount piv­otal study of Cabo/Op­di­vo com­bo for front­line kid­ney can­cer

Fouad Namouni, Bris­tol-My­ers Squibb

Just days af­ter re­view­ing a promis­ing start com­bin­ing Bris­tol-My­ers Squibb’s check­point in­hibitor Op­di­vo (nivolum­ab) with Cabome­tyx (cabozan­ti­nib), Ex­elix­is is rolling out a late-stage part­ner­ship that will take the com­bo in­to a piv­otal Phase III study as a front­line ther­a­py for kid­ney can­cer. And not sat­is­fied with the one check­point tie-up, the South San Fran­cis­co-based biotech al­so an­nounced a deal this morn­ing to col­lab­o­rate with Roche on a com­bi­na­tion of its drug Tecen­triq (ate­zolizum­ab) and cabo.

Ex­elix­is $EX­EL and Bris­tol-My­ers $BMY are split­ting the costs on their Phase III pro­gram, which will ex­plore the com­bo, ei­ther alone or with Yer­voy (ip­il­i­mum­ab), in kid­ney can­cer as well as blad­der can­cer, he­pa­to­cel­lu­lar car­ci­no­ma and pos­si­bly oth­er tu­mor types. The ear­ly stage work was done un­der an agree­ment with the NCI’s Can­cer Ther­a­py Eval­u­a­tion Pro­gram. This new pact marks Ex­elix­is’ and Bris­tol-My­ers’ first R&D col­lab­o­ra­tion in I/O.

Ex­elix­is shares jump 6% on the news.

Ten days ago Ex­elix­is un­veiled the first snap­shot of ef­fi­ca­cy da­ta for the dou­ble and triple com­bo in gen­i­touri­nary tu­mors.

In­ves­ti­ga­tors con­clud­ed:

Among the 43 pa­tients who were evalu­able for re­sponse, the ob­jec­tive re­sponse rate (ORR) for all tu­mor types was 30 per­cent (38 per­cent for the dou­blet dos­ing sched­ule and 18 per­cent for the triplet dos­ing sched­ule), with a 7 per­cent com­plete re­sponse (CR) rate and a 23 per­cent par­tial re­sponse (PR) rate. Sta­ble dis­ease (SD) was re­port­ed in 56 per­cent of pa­tients. The ORR for pa­tients with mUC was 38 per­cent, and 2 of 16 pa­tients achieved a CR, while 2 pa­tients with squa­mous cell car­ci­no­ma of the blad­der had ob­jec­tive re­spons­es (1 CR and 1 PR). In the mUC co­hort, 15 of 16 pa­tients had a CR, PR or SD as their best re­sponse.

“Com­bin­ing our Im­muno-On­col­o­gy port­fo­lio with promis­ing agents which tar­get dif­fer­ent and com­ple­men­tary path­ways is a key com­po­nent of our strat­e­gy to im­prove treat­ment out­comes for pa­tients,” said Fouad Namouni, MD, head of De­vel­op­ment, On­col­o­gy, Bris­tol-My­ers Squibb.

Bris­tol-My­ers — the one-time leader in check­point in­hibitors — is con­tin­u­ing to dou­ble down on Op­di­vo af­ter an em­bar­rass­ing se­ries of set­backs in lung can­cer bad­ly dent­ed its share price.

Leerink’s Michael Schmidt gave the deal a quick thumbs up, hap­py to see Ex­elix­is take a shot at mov­ing to front­line use.

This is pos­i­tive news since these col­lab­o­ra­tions could po­ten­tial­ly sig­nif­i­cant­ly ex­pand Cabome­tyx com­mer­cial po­ten­tial be­yond 2nd lien RCC, while lim­it­ing ad­di­tion­al in­cre­men­tal R&D spend which is in-line with mgmt.’s busi­ness strat­e­gy. While some of the Cabome­tyx opp’ty be­yond the cur­rent­ly ap­proved in­di­ca­tion in 2nd line RCC is re­flect­ed in our mod­el and val­u­a­tion, the scope of these col­lab­o­ra­tions ex­ceeds our ex­pec­ta­tions and could po­ten­tial­ly in­crease the reg­u­la­to­ry and com­mer­cial prob­a­bil­i­ty-of-suc­cess for Cabome­tyx in 1st line RCC. Our es­ti­mates are un­der re­view.

Ex­elix­is is al­so spon­sor­ing a Phase Ib study that pairs cabo with Tecen­triq in fight­ing sol­id tu­mors. With en­roll­ment planned to be­gin in the mid­dle of this year, in­ves­ti­ga­tors have a shot at lat­er open­ing up four treat­ment co­horts: one for pre­vi­ous­ly un­treat­ed ad­vanced clear cell re­nal cell car­ci­no­ma and three co­horts of urothe­lial car­ci­no­ma, in­clud­ing plat­inum el­i­gi­ble first-line pa­tients, first- or sec­ond-line plat­inum in­el­i­gi­ble pa­tients and pa­tients pre­vi­ous­ly treat­ed with plat­inum-con­tain­ing chemother­a­py.

The da­ta from these stud­ies can be made avail­able to Ex­elix­is’ part­ners, Ipsen and Take­da, for their own de­vel­op­ment ini­tia­tives, pro­vid­ed they opt in. So far though on­ly Ipsen has signed up.

“Peo­ple with ad­vanced gen­i­toruri­nary ma­lig­nan­cies are in need of ad­di­tion­al treat­ment op­tions that can im­prove clin­i­cal out­comes,” said Suman­ta Ku­mar Pal, MD, co-di­rec­tor, Kid­ney Can­cer Pro­gram at City of Hope, and prin­ci­pal in­ves­ti­ga­tor in the study. “The com­bined ap­proach of ty­ro­sine ki­nase in­hi­bi­tion with cabozan­ti­nib along­side im­mune-check­point in­hi­bi­tion has al­ready shown promise in an ear­ly phase 1 clin­i­cal tri­al. We look for­ward to fur­ther ex­am­in­ing this po­ten­tial with cabozan­ti­nib plus ate­zolizum­ab to treat a range of gen­i­touri­nary and oth­er tu­mors.”

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