Table 1. Agents included in the Signature Program.
| Agent | Target | Mutations Required | Tumor Types Excluded | ClinicalTrials.gov ID |
|---|---|---|---|---|
| Buparlisib (BKM120) [28] | Pan-Pl3K | PIK3CA mutation/amplification, PTEN mutation/loss, or PIK3R1 mutation | Endometrial, glioblastoma, NSCLC, prostate, breast | NCT01833169 |
| Dovitinib (TKI258) [29] | Various RTKs | FGFR1-3, FLT3, or c-KIT mutation/amplification or PDGFRα/β, VEGFR1-2, RET, TrkA (NTRK1), or CSF-1R mutation | Multiple myeloma, urothelial, AML (FLT3+), hepatocellular, endometrial, renal cell, breast (metastatic), squamous NSCLC | NCT01831726 |
| Binimetinib (MEK162)a [30] | MEK (RAS pathway) | RAS, RAF, MEK1/MEK2, or NF1 | Pancreatic, biliary, colorectal, ovarian (low-grade serous), melanoma | NCT01885195 |
| Encorafenib (LGX818)a [31] | BRAF | BRAF V600E | Melanoma, colorectal, primary CNS | NCT01981187 |
| Sonidegib (LDE225)b [32] | SMO (hedgehog pathway) | PTCH1 or SMO | Basal cell, pancreatic, medulloblastoma/primary CNS, CML, ALL, AML | NCT02002689 |
| BGJ398 [33] | FGFR | FGFR mutation/amplification/fusion, FGFR1-4 translocation, or ligand amplification | Urothelial, cholangiocarcinoma, glioblastoma multiforme | NCT02160041 |
| Ceritinib (LDK378)c [34] | ALK/ROS1 | ALK/ROS1 mutation/amplification/translocation/rearrangement | ALK+ NSCLC | NCT02186821 |
| Ribociclib (LEE011)d [35] | CDK4/6 | CDK4/6 mutation/amplification, cyclin D1/D3 amplification, or p16 mutation/loss | ER+ breast, mantle cell lymphoma, teratoma, liposarcoma, castration-resistant prostate, melanoma | NCT02187783 |
Abbreviations: ALK, anaplastic lymphoma kinase; ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; CDK, cyclin-dependent kinase; CML, chronic myeloid leukemia; CNS, central nervous system; CSF-1R, colony-stimulating factor 1 receptor; ER, estrogen receptor; FGFR, fibroblast growth factor receptor; FLT3, fms-related tyrosine kinase 3; MEK, mitogen-activated protein kinase/extracellular signal–regulated kinase kinase; NF1, neurofibromatosis type 1; NSCLC, non-small cell lung cancer; NTRK1, neurotrophic tyrosine kinase receptor type 1; PDGFR, platelet-derived growth factor receptor; PI3K, phosphatidylinositol 3-kinase; PIK3CA, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit α; PIK3R1, phosphatidylinositol 3-kinase regulatory subunit polypeptide 1; PTCH1, patched 1; PTEN, phosphatase and tensin homolog; RTK, receptor tyrosine kinase; SMO, smoothened; TrkA, tropomyosin receptor kinase A; VEGFR, vascular endothelial growth factor receptor.
aBinimetinib (MEK162) and encorafenib (LGX818) are owned by Array BioPharma.
bSonidegib (LDE225; Odomzo), owned by Sun Pharmaceuticals, is a hedgehog pathway inhibitor indicated for the treatment of adult patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy or those who are not candidates for surgery or radiation therapy [36].
cCeritinib (LDK378) is approved by the US Food and Drug Administration for the second-line treatment of ALK+ NSCLC [37].
dRibociclib (LEE011; Kisqali) was discovered by the Novartis Institutes for Biomedical Research in collaboration with Astex Pharmaceuticals. Kisqali is a kinase inhibitor indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced or metastatic breast cancer [38].