Metastatic Non-Small Cell Lung Cancer

Also known as: Metastatic untreated non small cell lung cancer / Non-Small Cell Lung Cancer Metastatic / Metastatic Non-small Cell Lung Cancer (NSCLC) / Metastatic Non-Small-Cell Lung Cancer / Lung cancer non-small cell stage IV / Non-small cell lung cancer stage IV

DrugDrug NameDrug Description
DB08916AfatinibAfatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor in the form of a dimaleate salt available as Boehringer Ingelheim's brand name Gilotrif [FDA Label]. For oral use, afatinib tablets are a first-line (initial) treatment for patients with metastatic non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test [L2939]. Gilotrif (afatinib) is the first FDA-approved oncology product from Boehringer Ingelheim [L2939].
DB11595AtezolizumabAtezolizumab is an Fc-engineered, humanized, monoclonal antibody that binds to Programmed Death Ligand 1 (PD-L1) and blocks its interactions with the receptors B7.1 (also known as CD80) and Programmed Death 1 (PD-1). The binding of PD-L1 to PD-1 or B7.1 on activated T cells causes an inhibitory signal to suppress their production in the lymph nodes, thereby preventing immune responses to events such as pregnancy or autoimmune disease. This pathway is also utilized by cancer cells to evade the immune system through evasion of anti-tumor T-cell response. Furthermore, over-expression of PD-L1 and PD-1 has been linked to increased tumour aggressiveness and poorer prognosis. Currently the only antibody against PD-L1 and available as the product Tecentriq (FDA), atezolizumab is indicated for the treatment of locally advanced or metastatic urothelial carcinoma.
DB12267BrigatinibBrigatinib, originally named AP26113, is a reversible dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It presents selectivity against the mutant forms of EGFR compared to the wild-type.[A31311] It also exhibits selectivity against 9 different Crizotinib-resistant mutants of the EML4-ALK fusion gene, which is a pivotal player in the transformation of susceptible lung parenchyma.[A31313] Brigatinib was developed by Ariad Pharmaceuticals, a subsidiary of Takeda Pharmaceutical Company Limited, and FDA-approved on April 28, 2017.[L1026]
DB08865CrizotinibCrizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011.
DB11963DacomitinibDacomitinib, designed as (2E)-N-16-4-(piperidin-1-yl) but-2-enamide, is an oral highly selective quinazalone part of the second-generation tyrosine kinase inhibitors which are characterized by the irreversible binding at the ATP domain of the epidermal growth factor receptor family kinase domains.[A40009] Dacomitinib was developed by Pfizer Inc and approved by the FDA on September 27, 2018.[L4810] Some evidence in the literature suggests the therapeutic potential of dacomitinib in the epithelial ovarian cancer model[A39624], although further investigations are needed.
DB01248DocetaxelDocetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of one mole docetaxel per mole tubulin in microtubules.
DB00530ErlotinibErlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.
DB00317GefitinibGefitinib (originally coded ZD1839) is a drug used in the treatment of certain types of cancer. Acting in a similar manner to erlotinib (marketed as Tarceva), gefitinib selectively targets the mutant proteins in malignant cells. It is marketed by AstraZeneca under the trade name Iressa.
DB09559NecitumumabNecitumumab is an intravenously administered recombinant monoclonal IgG1 antibody used in the treatment of non-small cell lung cancer (NSCLC) as an EGFR antagonist. It functions by binding to epidermal growth factor receptor (EGFR) and prevents binding of its ligands, a process that is involved in cell proliferation, metastasis, angiogenesis, and malignant progression. Binding of necitumumab to EGFR induces receptor internalization and degradation, thereby preventing further activation of EGFR which is beneficial in NSCLC as many patients have increased protein expression of EGFR. Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC).
DB09330OsimertinibOsimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug developed by AstraZeneca Pharmaceuticals. Its use is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in cases where tumour EGFR expression is positive for the T790M mutation as detected by FDA-approved testing and which has progressed following therapy with a first-generation EGFR tyrosine kinase inhibitor. Approximately 10% of patients with NSCLC have a rapid and clinically effective response to EGFR-TKIs due to the presence of specific activating EGFR mutations within the tumour cells. More specifically, deletions around the LREA motif in exon 19 and exon 21 L858R point mutations are correlated with response to therapy. Development of third-generation EGFR-TKIs, such as osimertinib, has been in response to altered tumour resistance patterns following treatment and toxic side effects that impact patient quality of life. Treatment with first-generation EGFR-TKIs (gefitinib and erlotinib) has been associated with the development of resistance through activating mutations in the EGFR gene. Second-generation EGFR-TKIs (afatinib and dacomitinib) were then developed to be more potent inhibitors, although their use is associated with increased toxicity through nonspecific targeting of wild-type EGFR. In contrast, third-generation inhibitors are specific for the gate-keeper T790M mutations which increases ATP binding activity to EGFR and result in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.
DB01229PaclitaxelPaclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. When it was developed commercially by Bristol-Myers Squibb (BMS), the generic name was changed to paclitaxel and the BMS compound is sold under the trademark Taxol. In this formulation, paclitaxel is dissolved in Kolliphor EL and ethanol, as a delivery agent. A newer formulation, in which paclitaxel is bound to albumin, is sold under the trademark Abraxane. [Wikipedia]
DrugDrug NameTargetType
DB08916AfatinibEpidermal growth factor receptortarget
DB08916AfatinibReceptor tyrosine-protein kinase erbB-2target
DB08916AfatinibReceptor tyrosine-protein kinase erbB-4target
DB08916AfatinibMultidrug resistance protein 1transporter
DB08916AfatinibATP-binding cassette sub-family G member 2transporter
DB11595AtezolizumabProgrammed cell death 1 ligand 1target
DB12267BrigatinibALK tyrosine kinase receptortarget
DB12267BrigatinibEpidermal growth factor receptortarget
DB12267BrigatinibTyrosine-protein kinase ABL1target
DB12267BrigatinibInsulin-like growth factor 1 receptortarget
DB12267BrigatinibReceptor-type tyrosine-protein kinase FLT3target
DB12267BrigatinibCytochrome P450 2C8enzyme
DB12267BrigatinibCytochrome P450 3A4enzyme
DB12267BrigatinibInsulin receptortarget
DB12267BrigatinibHepatocyte growth factor receptortarget
DB12267BrigatinibReceptor tyrosine-protein kinase erbB-4target
DB12267BrigatinibReceptor tyrosine-protein kinase erbB-2target
DB12267BrigatinibATP-binding cassette sub-family B member 5transporter
DB12267BrigatinibATP-binding cassette sub-family G member 2transporter
DB12267BrigatinibSolute carrier family 22 member 1transporter
DB12267BrigatinibMultidrug and toxin extrusion protein 1transporter
DB12267BrigatinibMultidrug and toxin extrusion protein 2transporter
DB08865CrizotinibCytochrome P450 3A4enzyme
DB08865CrizotinibCytochrome P450 3A5enzyme
DB08865CrizotinibMultidrug resistance protein 1transporter
DB08865CrizotinibALK tyrosine kinase receptortarget
DB08865CrizotinibHepatocyte growth factor receptortarget
DB08865CrizotinibCytochrome P450 2B6enzyme
DB11963DacomitinibCytochrome P450 2D6enzyme
DB11963DacomitinibSerum albumincarrier
DB11963DacomitinibCytochrome P450 3A4enzyme
DB11963DacomitinibCytochrome P450 2C9enzyme
DB11963DacomitinibUDP-glucuronosyltransferase 1-1enzyme
DB11963DacomitinibMultidrug resistance protein 1transporter
DB11963DacomitinibATP-binding cassette sub-family G member 2transporter
DB11963DacomitinibSolute carrier family 22 member 1transporter
DB11963DacomitinibEpidermal growth factor receptortarget
DB01248DocetaxelApoptosis regulator Bcl-2target
DB01248DocetaxelTubulin beta-1 chaintarget
DB01248DocetaxelCytochrome P450 3A4enzyme
DB01248DocetaxelCytochrome P450 3A5enzyme
DB01248DocetaxelCytochrome P450 3A7enzyme
DB01248DocetaxelMultidrug resistance protein 1transporter
DB01248DocetaxelMultidrug resistance-associated protein 7transporter
DB01248DocetaxelCytochrome P450 1B1enzyme
DB01248DocetaxelMicrotubule-associated protein 2target
DB01248DocetaxelMicrotubule-associated protein 4target
DB01248DocetaxelMicrotubule-associated protein tautarget
DB01248DocetaxelSolute carrier organic anion transporter family member 1B3transporter
DB01248DocetaxelSolute carrier family 22 member 7transporter
DB01248DocetaxelATP-binding cassette sub-family G member 2transporter
DB01248DocetaxelCanalicular multispecific organic anion transporter 1transporter
DB01248DocetaxelMultidrug resistance-associated protein 1transporter
DB01248DocetaxelNuclear receptor subfamily 1 group I member 2target
DB00530ErlotinibEpidermal growth factor receptortarget
DB00530ErlotinibCytochrome P450 3A4enzyme
DB00530ErlotinibATP-binding cassette sub-family G member 2transporter
DB00530ErlotinibMultidrug resistance protein 1transporter
DB00530ErlotinibNuclear receptor subfamily 1 group I member 2target
DB00530ErlotinibCytochrome P450 3A5enzyme
DB00530ErlotinibCytochrome P450 1A1enzyme
DB00530ErlotinibCytochrome P450 1A2enzyme
DB00530ErlotinibCytochrome P450 1B1enzyme
DB00530ErlotinibCytochrome P450 2D6enzyme
DB00530ErlotinibCytochrome P450 2C8enzyme
DB00530ErlotinibUDP-glucuronosyltransferase 1-1enzyme
DB00530ErlotinibSerum albumincarrier
DB00530ErlotinibAlpha-1-acid glycoprotein 1carrier
DB00530ErlotinibSolute carrier organic anion transporter family member 2B1transporter
DB00317GefitinibEpidermal growth factor receptortarget
DB00317GefitinibCytochrome P450 3A4enzyme
DB00317GefitinibCytochrome P450 2D6enzyme
DB00317GefitinibMultidrug resistance protein 1transporter
DB00317GefitinibATP-binding cassette sub-family G member 2transporter
DB00317GefitinibCytochrome P450 3A5enzyme
DB00317GefitinibCytochrome P450 1A1enzyme
DB00317GefitinibCytochrome P450 2C9enzyme
DB00317GefitinibCytochrome P450 2C19enzyme
DB00317GefitinibSerum albumincarrier
DB00317GefitinibAlpha-1-acid glycoprotein 1carrier
DB09559NecitumumabEpidermal growth factor receptortarget
DB09330OsimertinibEpidermal growth factor receptortarget
DB09330OsimertinibMultidrug resistance protein 1transporter
DB09330OsimertinibATP-binding cassette sub-family G member 2transporter
DB09330OsimertinibCytochrome P450 3A4enzyme
DB09330OsimertinibCytochrome P450 1A2enzyme
DB01229PaclitaxelApoptosis regulator Bcl-2target
DB01229PaclitaxelTubulin beta-1 chaintarget
DB01229PaclitaxelCytochrome P450 2C8enzyme
DB01229PaclitaxelCytochrome P450 3A4enzyme
DB01229PaclitaxelCytochrome P450 3A5enzyme
DB01229PaclitaxelCytochrome P450 3A7enzyme
DB01229PaclitaxelBile salt export pumptransporter
DB01229PaclitaxelMultidrug resistance protein 1transporter
DB01229PaclitaxelMultidrug resistance-associated protein 1transporter
DB01229PaclitaxelMultidrug resistance-associated protein 7transporter
DB01229PaclitaxelCytochrome P450 19A1enzyme
DB01229PaclitaxelCytochrome P450 1B1enzyme
DB01229PaclitaxelSolute carrier organic anion transporter family member 1B3transporter
DB01229PaclitaxelNuclear receptor subfamily 1 group I member 2target
DB01229PaclitaxelMicrotubule-associated protein 4target
DB01229PaclitaxelMicrotubule-associated protein 2target
DB01229PaclitaxelMicrotubule-associated protein tautarget
DB01229PaclitaxelATP-binding cassette sub-family G member 2transporter
DB01229PaclitaxelCanalicular multispecific organic anion transporter 1transporter
DrugDrug NamePhaseStatusCount
DB00531Cyclophosphamide1Active Not Recruiting1
DB09037Pembrolizumab1Active Not Recruiting1
DB05220Alisertib1 / 2Terminated1
DB11945Avelumab1 / 2Recruiting1
DB06626Axitinib1 / 2Recruiting1
DB11714Durvalumab1 / 2Recruiting1
DB00530Erlotinib1 / 2Terminated1
DB09073Palbociclib1 / 2Recruiting1
DB11771Tremelimumab1 / 2Recruiting1
DB12247AZD-45472Active Not Recruiting1
DB12218AZD-53632Active Not Recruiting1
DB11714Durvalumab2Active Not Recruiting1
DB11717Epacadostat2Active Not Recruiting2
DB09074Olaparib2Active Not Recruiting1
DB09037Pembrolizumab2Active Not Recruiting2
DB00642Pemetrexed2Active Not Recruiting1
DB12183Sapitinib2Active Not Recruiting1
DB12048Savolitinib2Active Not Recruiting1
DB11689Selumetinib2Active Not Recruiting1
DB04900Thymalfasin2Not Yet Recruiting1
DB05294Vandetanib2Active Not Recruiting1
DB11925Vistusertib2Active Not Recruiting1
DB01248Docetaxel2 / 3Terminated1
DB00515Cisplatin3Active Not Recruiting2
DB00530Erlotinib3Active Not Recruiting1
DB00317Gefitinib3Active Not Recruiting1
DB00441Gemcitabine3Active Not Recruiting2
DB06186Ipilimumab3Not Yet Recruiting1
DB09035Nivolumab3Not Yet Recruiting1
DB09330Osimertinib3Active Not Recruiting1
DB00642Pemetrexed3Active Not Recruiting1
DB05578Ramucirumab3Active Not Recruiting1