This week in therapeutics




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Lung cancer

Programmed cell death 1 (PDCD1;
PD-1; CD279); programmed cell death 1 ligand 1 (CD274 molecule; PD-L1; B7-H1); epidermal growth factor receptor (EGFR)

Primary tumor and mouse studies suggest inhibitors of PD-1 and PD-L1 could help treat lung cancer harboring EGFR mutations. In primary lung tumors and transgenic mouse models of lung cancer, mutations in EGFR were associated with increased expression of PD-1 or PD-L1. In transgenic mouse models with EGFR mutations, a murine anti-Pd-1 mAb decreased tumor growth and increased survival compared with no treatment. Ongoing work includes testing combinations of EGFR and PD-1 or
PD-L1 inhibitors in mouse models of lung cancer.
Ono Pharmaceutical Co. Ltd. and Bristol-Myers Squibb Co. have nivolumab (ONO-4538; MDX-1106; BMS-936558), a human mAb against PD-1, in Phase III testing to treat non-small cell lung cancer (NSCLC), renal cancer and melanoma and in Phase I testing to treat liver cancer and solid tumors.
Roche and its Genentech Inc. unit have RG7446 (MPDL3280A), a human mAb against PD-L1, in Phase II
testing to treat NSCLC and Phase I testing to treat melanoma and solid tumors.
Merck & Co. Inc. has MK-3475, an anti-PD-1 mAb, in Phase II/III trials to treat NSCLC and in Phase III testing to treat melanoma.
At least five other companies have anti-PD-1 or anti-PD-L1 antibodies in Phase II or earlier development.

SciBX 6(41); doi:10.1038/scibx.2013.1159
Published online Oct. 24, 2013

Unpatented; unlicensed; available for partnering

Akbay, E.A. et al. Cancer Discov.; published online Sept. 27, 2013;
Contact: Kwok-Kin Wong, Dana-Farber Cancer Institute, Boston, Mass.