Colon Cancer Data Key As Pfizer Buys Array

Published OnlineFirst June 21, 2019; DOI: 10.1158/2159-8290.CD-NB2019-075

NEWS IN BRIEF

PEOPLE of disease. Patients often receive ing factor-1 receptor in a phase II irinotecan-containing chemotherapy combination trial with pembroli- Hans Bishop began regimens plus the EGFR inhibitor zumab (Keytruda; Merck) for patients his role as CEO of cetuximab (Erbitux; Eli Lilly)—but with advanced solid tumors, as well as Grail on June 7, replac- encorafenib and binimetinib plus a portfolio of royalty-generating medi- ing Jennifer Cook, cetuximab looks to be a signifi cantly cines that originated with Array before MBA, who stepped better option. the company licensed them to others. down . Previously, he In May, Array reported interim The royalty-generating assets founded Juno Thera- results from the phase III BEACON include two marketed drugs, the TRK

Grail, Inc. Grail, peutics, serving as trial, which enrolled patients with inhibitor larotrectinib (Vitrakvi; Bayer) president and CEO until the company was colorectal cancer whose disease pro- approved in the United States last acquired by Celgene in 2018 and he joined gressed despite treatment. (No other year, and danoprevir (Ganovo; Roche), its board of directors . Bishop was also a co- companies have advanced BRAF–MEK a hepatitis C drug available in China, founder and the executive chairman of inhibitor combinations past phase II for plus a handful of late-stage clinical Sana Biotechnology, the chairman of Lyell this indication.) The data showed that candidates—the AKT inhibitor ipata- ImmunoPharma, and a director of Agilent Array’s chemotherapy-free triplet regi- sertib (Genentech), the MEK inhibitor Technologies . He has held various other men produced higher overall response selumetinib (AstraZeneca), the HER2 executive roles at Dendreon, Bayer, Chiron rates (26% versus 2%) and longer overall inhibitor tucatinib (Seattle Genetics), Corp ., and European Biopharmaceuticals . survival times (9 months versus 5.4 and the RET inhibitor LOXO-292 months) compared with cetuximab and (Loxo/Eli Lilly). –Elie Dolgin n chemotherapy. Colon Cancer Data Key Array has said it intends to submit the data to U.S. regulators later this AMG 510 First to Inhibit as Pfizer Buys Array year, around the same time as the “Undruggable” KRAS Last month, Array BioPharma deal with Pfi zer is expected to close. Amgen’s novel small-molecule announced that a pair of their drugs Meanwhile, Array is also evaluating its inhibitor AMG 510 has become the could dramatically improve outcomes BRAF–MEK combo in patients with fi rst drug to show activity in patients for some patients with advanced BRAF-mutant non–small cell lung can- with KRASG12C-mutant solid tumors. colorectal cancer. Now, Pfi zer has cer and as a fi rst-line treatment with In a phase I trial, AMG 510 elicited announced plans to acquire the Boulder, cetuximab for BRAF-mutant colorectal partial responses in half of patients CO–based drugmaker in a deal valued cancer. with non–small cell lung cancer at approximately $11.4 billion—and to In a statement, Pfi zer CEO Albert (NSCLC) and led to stable disease in maintain the company as a stand-alone Bourla, DVM, PhD, said the acqui- patients with colorectal or appendix research unit. sition of Array’s BRAF and MEK cancer. The striking results were pre- The agreement, unveiled on June 17, inhibitors “sets the stage to create a will give Pfi zer two drugs, encorafenib potentially industry-leading franchise sented at the 2019 American Society of (Braftovi) and binimetinib (Mektovi), for colorectal cancer.” However, the Clinical Oncology Annual Meeting in approved by the FDA last year for fi nancial benefi ts could take years to Chicago, IL, in June (J Clin Oncol 37, patients with BRAF-mutant metastatic accrue, with encorafenib and bini- 2019 [suppl; abstr 3003]). melanoma. Compared with other metinib not projected to cross the “This is a population of patients BRAF–MEK inhibitor combinations, the $1 billion annual threshold until the that has not had targeted therapies, Array regimen is “better [than] or tied middle of the next decade, with about and the fact that they’re now poten- for best-in-class” in terms of effi cacy and half the revenue stemming from a tially being included in that approach safety, according to Keith Flaherty, MD, colorectal cancer–label expansion. is really a remarkable thing,” said Pasi of the Massachusetts General Hospital Ironically, the regimen could soon A. Jänne, MD, PhD, of Dana-Farber Cancer Center in Boston, MA, who led face competition from a Pfi zer spin-off Cancer Institute/Harvard Cancer the drugs’ clinical testing. company called SpringWorks Thera- Center in Boston, MA, who was not However, as this is the third BRAF– peutics. On June 18, BeiGene and involved in the trial. MEK inhibitor combination to reach SpringWorks announced the creation KRAS alterations are the most the market for melanoma, that indica- of a joint venture called MapKure that prevalent oncogenic driver mutations tion is unlikely to generate substantial will advance BeiGene’s BRAF inhibi- in cancer. However, researchers have revenues for Pfi zer. What could push tor, BGB-3245, likely in combination long considered KRAS undruggable up sales of encorafenib–binimetinib with a former Pfi zer asset, the MEK due to its small size and relatively is a supplemental approval for the inhibitor PD-0325901. smooth surface—with few deep pock- treatment of BRAF-mutant metastatic Pfi zer gains more in the deal than ets where molecules can bind—as well colorectal cancer. encorafenib and binimetinib, however. as how rapidly and tightly it binds Currently, no drug regimens are For example, the sale includes ARRY- to GTP in its active state. AMG 510 specifi cally indicated for this type 382, an inhibitor of colony-stimulat- binds to KRASG12C via the cysteine

988 | CANCER DISCOVERY AUGUST 2019 www.aacrjournals.org

Colon Cancer Data Key as Pfizer Buys Array

Cancer Discov 2019;9:988. Published OnlineFirst June 21, 2019.

Updated version Access the most recent version of this article at: doi:10.1158/2159-8290.CD-NB2019-075

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