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Abbreviations:

4-1BB, tumor necrosis factor receptor superfamily member 9; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; APRIL, a proliferation inducing ligand; BAFF, B-cell activating factor from the tumor necrosis factor family; BAK, Bcl-2 homologous antagonist killer; BAX, Bcl-2-associated X protein; BCL-2, B-cell lymphoma 2; BCMA, B-cell maturation antigen; BCR, B-cell receptor; BH, Bcl-2 homology domain; BiTE, Bispecific T-cell Engager; C5, complement component 5; CD, cluster of differentiation; CIT, chemotherapy-induced thrombocytopenia; CLDN18.2, Claudin-18 isoform 2; DARPin, designed ankyrin repeat proteins; DLBCL, diffuse large B-cell lymphoma; DLL3, delta-like protein 3; EGFR, epidermal growth factor receptor; EGFRvIII, epidermal growth factor receptor variant III; Fab, fragment antigen-binding; FAP, fibroblast activation protein; Fc, fragment crystallizable; FLT3, fms-like tyrosine kinase 3; GEJ, gastroesophageal junction; GM-CSF, granulocyte-macrophage colony-stimulating factor; GvHD, graft versus host disease; HCC, hepatocellular carcinoma; HLE, half-life extended; IL-2R, interleukin 2 receptor; IL-21R, interleukin 21 receptor; IL-2Rα, interleukin 2 receptor alpha; KRAS, Kirsten rat sarcoma; MAC, membrane attack complex; MCL-1, myeloid cell leukemia-1; mCRPC, metastatic castration-resistant prostate cancer; MetMel, metastatic melanoma; MM, multiple myeloma; MOA, mechanism of action; MUC17, mucin 17; NHL, non-Hodgkin's lymphoma; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; PD-L2, programmed cell death ligand 2; PNH, paroxysmal nocturnal hemoglobinuria; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen; RAS, rat sarcoma; R/R, relapsed or refractory; SCLC, small cell lung cancer; STEAP1, six-transmembrane epithelial antigen of prostate 1; TPO, thrombopoietin; TPO-R, thrombopoietin receptor; Treg, regulatory T cell.

Amgen Oncology
Pipeline

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SOLID MALIGNANCIES

MALIGNANCIES

TARGETS

HEMATOLOGIC DISEASES

DISEASES

TARGETS

PIPELINE

BITE® PLATFORM

BIOSIMILARS

MODALITIES

KRASG12C

KRAS, a member of the RAS family, is a key regulator of signaling pathways responsible for cell proliferation, differentiation, and survival.1,2 The RAS gene family comprises the most frequently mutated oncogenes in human cancer. Within the RAS family, KRAS is the most prevalent form.1 The normal KRAS protein cycles between an active and inactive form, regulating normal cell proliferation, differentiation, and survival. KRAS G12C is a single point mutation of the KRAS gene, where cysteine is substituted for glycine at codon 12.1,3-5 The KRAS G12C mutation, however, favors the active form of the KRAS mutant protein, which supports oncogenic signaling and tumorigenesis.1,4,6

KRAS, Kirsten rat sarcoma; MOA, mechanism of action; NSCLC, non-small cell lung cancer; RAS, rat sarcoma.

References
1. Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851. 2. Downward J. Nat Rev Cancer. 2003;3:11-22. 3. Biernacka A, et al. Cancer Genet. 2016;209:195-198. 4. Ryan MB, et al. Nat Rev Clin Oncol. 2018;15:709-720. 5. Ihle NT, et al. J Natl Cancer Inst. 2012;104:228-239. 6. Simanshu DK, et al. Cell. 2017;170:17-33. 7. Amgen Pipeline. https://www.amgenpipeline.com. Accessed 9/10/20. 8. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT03600883. Accessed 9/10/20. 9. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT04185883. Accessed 9/10/20. 10. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT04303780. Accessed 9/10/20.
Molecule
Modality7
Target7
Areas of Investigation8-10
Sotorasib
Target7
KRASG12C
Areas of Investigation8-10

KRAS, Kirsten rat sarcoma; MOA, mechanism of action; NSCLC, non-small cell lung cancer; RAS, rat sarcoma.

References
1. Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851. 2. Downward J. Nat Rev Cancer. 2003;3:11-22. 3. Biernacka A, et al. Cancer Genet. 2016;209:195-198. 4. Ryan MB, et al. Nat Rev Clin Oncol. 2018;15:709-720. 5. Ihle NT, et al. J Natl Cancer Inst. 2012;104:228-239. 6. Simanshu DK, et al. Cell. 2017;170:17-33. 7. Amgen Pipeline. https://www.amgenpipeline.com. Accessed 9/10/20. 8. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT03600883. Accessed 9/10/20. 9. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT04185883. Accessed 9/10/20. 10. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT04303780. Accessed 9/10/20.

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