WO2017201142A1 - Traitement de l'adénocarcinome du poumon - Google Patents

Traitement de l'adénocarcinome du poumon Download PDF

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WO2017201142A1
WO2017201142A1 PCT/US2017/033062 US2017033062W WO2017201142A1 WO 2017201142 A1 WO2017201142 A1 WO 2017201142A1 US 2017033062 W US2017033062 W US 2017033062W WO 2017201142 A1 WO2017201142 A1 WO 2017201142A1
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subject
tnf
certolizumab
inhibitor
lung adenocarcinoma
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PCT/US2017/033062
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Paul PAIK
Joan Massague
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Memorial Sloan Kettering Cancer Center
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Definitions

  • Lung cancer is the most common cause of cancer death worldwide. Despite newer targeted therapy options, lung cancer survival statistics are still discouraging. For example, the cure rate for stage I non-small cell lung cancer (NSCLC) is 60% and for stage IIIA NSCLC is just 20% (1).
  • NSCLC non-small cell lung cancer
  • the present invention is based, in part, on a series of discoveries relating to the role of TNF-a, CXCLl/2, and/or S100A8/9 in lung adenocarcinoma, and relating to the effects of inhibitors of some of such molecules on lung adenocarcinomas in human subjects - as described in more detail in the Examples section of this patent specification. Building on these discoveries the present invention provides certain new methods and compositions for the treatment of lung adenocarcinoma.
  • the present invention provides methods for treating lung adenocarcinoma, such methods comprising administering to subjects in need thereof an effective amount of either: (a) a TNF-a inhibitor, (b) a CXCLl/2 inhibitor, or (c) a S100A8/9 inhibitor, or any combination thereof.
  • the present invention provides methods for treating lung adenocarcinoma, such methods comprising administering to subjects in need thereof an effective amount of a TNF- a inhibitor.
  • such methods further comprise administering to the subject an effective amount of one or more chemotherapeutic agents.
  • both a platinum-based chemotherapeutic agent and a non-platinum-based chemotherapeutic agent are administered.
  • the present invention provides methods for treating lung adenocarcinoma, such methods comprising administering to subjects in need thereof an effective amount of a TNF- a inhibitor and an effective amount of one or more
  • the present invention provides methods for treating lung adenocarcinoma, such methods comprising administering to subjects in need thereof an effective amount of a TNF- a inhibitor, an effective amount of a platinum-based chemotherapeutic agent, and an effective amount of a non-platinum-based chemotherapeutic agent.
  • present invention provides pharmaceutical compositions comprising an effective amount of (a) a TNF- a inhibitor, a CXCLl/2 inhibitor, or a
  • compositions comprise a TNF- a inhibitor and one or more chemotherapeutic agents.
  • compositions comprise a TNF- a inhibitor, a platinum-based chemotherapeutic agent, and a non-platinum-based
  • TNF- a inhibitors examples include, but are not limited to, certolizumab, certolizumab pegol (Cimzia), infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi), thalidomide (Immunoprin), lenalidomide (Revlimid), xanthine derivatives, pentoxifylline, and bupropion.
  • the TNF- a inhibitor is a TNF- a inhibitory antibody.
  • the TNF- a inhibitor is a TNF- a inhibitory antibody selected from the group consisting of certolizumab, certolizumab pegol (Cimzia), infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi).
  • the TNF- a inhibitor is the TNF- a inhibitory antibody certolizumab (e.g.
  • platinum -based chemotherapeutic agents examples include, but are not limited to, cisplatin and carboplatin.
  • paclitaxel include, but are not limited to, paclitaxel, gemcitabine, and pemetrexed.
  • FIG. 1 Prominent copy number gain of S100A9 gene in lung adenocarcinomas. S100A9 gene copy number was determined by Oncomine analysis from dataset from among 51 different cancer types.
  • Fig. 2 Paraffin tissue microarray samples were immunostained with an antibody against S100A8/9.
  • Lung cancer subtypes include Muco-epidermoid (Muco-epi), Large Cell, Squamous, Bronchio-alveloar (Bralveo) and lung adenocarcinoma (Adenoca). S100A8/9 expression was highest in Adenoca.
  • Fig. 3A-B Gene expression of CXCLl/2 and S100A8/9 in metastatic lung cancer cells. Metastatic derivatives were isolated from three rounds of in-vivo selection of two adenocarcinoma cell lines, H2030 and PC9. Relative gene expression of the indicated genes were tested by qRT-PCR analysis in parental and metastatic H2030 (Fig. 3A) and PC9 (Fig. 3B) adenocarcinoma cell lines.
  • FIG. 4 RAGE (S100A8 receptor) knockdown inhibits metastasis formation in PC9 lung adenocarcinoma cells selected for brain metastatic potential.
  • N 3 mice per condition, photon flux was assessed 4 weeks after intracardiac injection of cells.
  • the left panel is a graph showing photon flux after injection of control PC9 cells or cells treated with the RAGE shRNA.
  • the two right-hand panels show photon flux images in from mice injected with control PC9 cells (middle panel) or cells treated with the RAGE shRNA (right-hand panel).
  • an “active agent” is an agent (e.g. a small molecule, or a protein/peptide - such as an antibody), for example as described and/or claimed herein, that has the recited activity - such as TNF-a inhibitory activity, CXCLl/2- inhibitory activity, S100A8/9- inhibitory activity, or chemotherapeutic activity.
  • Active agents include, but are not limited to, the specific inhibitors described in this patent disclosure. It is also contemplated that, in each of the embodiments of the present patent disclosure that involve use of specified active agents, analogues, variants, or derivatives of each of such specified active agents can be used.
  • an analogue, variant, or derivative of any of such specified active agent is suitable for use in accordance with the compositions and methods of the present invention, for example based on whether the analogue, variant, or derivative has one or more of the desired activities, such as, for example, TNF-a inhibitory activity, CXCLl/2- inhibitory activity, S100A8/9- inhibitory activity, or chemotherapeutic activity.
  • active agents can be antibodies.
  • antibody encompasses intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab', F(ab')2, and Fv, and single chain Fv (scFv) fragments, single-domain antibodies (sdAb or nanobodies)), fusion proteins comprising an antigen determination portion of an antibody, bispecific antibodies generated from at least two intact antibodies, chimeric antibodies, humanized antibodies, human antibodies, and any other modified immunoglobulin molecule(s) comprising an antigen recognition site - so long as the antibodies have the desired and/or recited biological activity - such as TNF-a inhibitory activity.
  • An antibody can be of any the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g.
  • IgGl, IgG2, IgG3, IgG4, IgAl and IgA2) based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively.
  • the different classes of immunoglobulins have different and well-known subunit structures and three-dimensional configurations.
  • Antibodies can be naked, or conjugated to other molecules such as toxins, radioisotopes, or any of the other specific molecules recited herein.
  • inhibitor refers to any statistically significant decrease in biological activity, including - but not limited to - full blocking of the activity.
  • Certolizumab is the antibody (Fab fragment of a humanized recombinant monoclonal antibody) to TNFa that is the active component of the certolizumab pegol product currently sold in the U.S. under the tradename Cimzia.
  • the term “certolizumab” includes certolizumab linked to polyethylene glycol or "certolizumab pegol.” Thus, wherever the term “certolizumab” is used,
  • certolizumab pegol is included. Furthermore, one of skill in the art will appreciate that, in those embodiments that refer specifically to “certolizumab pegol,” non-pegylated
  • certolizumab may also be used.
  • the certolizumab antibody is well known in the art, and it can be made, formulated, and used as described in the art. [00026] Various other terms are defined elsewhere in this patent disclosure, where used. Furthermore, terms that are not specifically defined herein may be more fully understood in the context in which the terms are used and/or by reference to the specification in its entirety. Where no explicit definition is provided, all technical and scientific terms used herein have the meanings commonly understood by those of ordinary skill in the art to which this invention pertains.
  • the present invention provides methods for the treatment of lung adenocarcinomas that comprise administration of one or more TNF-a inhibitors.
  • the present invention provides compositions comprising one or more TNF-a inhibitors.
  • any suitable TNF-a inhibitor can be used.
  • the suitability of a TNF-a inhibitor for use in accordance with the methods of the present invention may be ascertained from the literature (for example from published studies demonstrating anti-TNF-a activity), or may be ascertained by employing various assays for anti- TNF-a activity or anti-tumor activity, such as those described in the Examples section of the present patent application and/or those known in the art.
  • TNF-a inhibitors that are known in the art can be used in conjunction with the present invention.
  • any one or more of the following TNF-a inhibitors may be used: certolizumab, certolizumab pegol (Cimzia), infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi), thalidomide (Immunoprin), lenalidomide (Revlimid), xanthine derivatives, pentoxifylline, and bupropion.
  • the TNF-a inhibitor may be a small molecule.
  • the TNF-a inhibitor may be an antibody.
  • the TNF-a inhibitor may be other suitable agent that has TNF-a inhibitory activity.
  • any suitable variant, analogue or derivative of any one of such TNF-a inhibitors may be used.
  • the TNF-a inhibitor may be linked to, or capable or co-delivery with, another agent that can confer upon the TNF-a inhibitor the ability to target a lung tumor, or lung tumor cells.
  • the present invention provides methods for the treatment of lung adenocarcinomas that comprise administration of a CXCLl/2 inhibitor.
  • a CXCLl/2 inhibitor such as the CXCLl/2 receptor referred to as CXCR2
  • CXCR2 the CXCLl/2 receptor referred to as CXCR2
  • any suitable CXCLl/2 inhibitor or CXCLl/2 receptor inhibitor known in the art may be used.
  • the present invention provides methods for the treatment of lung adenocarcinomas that comprise administration of a S100A8/9 inhibitor.
  • a S100A8/9 inhibitor such as the S100A8/9 receptor referred to as RAGE
  • any suitable S100A8/9 inhibitor or S100A8/9 receptor inhibitor known in the art may be used.
  • the present invention provides methods for the treatment of lung adenocarcinomas that comprise administration to a subject of or more TNF-a inhibitors, CXCLl/2 inhibitors, and/or S100A8/9 inhibitors, and also administration to the subject of one or more additional active agents useful in the treatment of lung adenocarcinomas, for example chemotherapeutic agents or other active agents.
  • the methods of the present invention may involve administration of one or more
  • chemotherapeutic agents selected from the group consisting of: cisplatin, carboplatin, gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide and/or vinorelbine.
  • chemotherapeutic agents selected from the group consisting of: cisplatin, carboplatin, gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide and/or vinorelbine.
  • platinum-based chemotherapeutic agents such as cisplatin or carboplatin
  • non-platinum-based chemotherapeutic agents such as gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide and/or vinorelbine
  • the methods of the present invention may involve administration of one or more non-chemotherapeutic agents, such as, for example, erlotinib (Tarceva), gefitinib, afatinib (Gilotrif), denosumab, bevacizumab (Avastin), ceritinib (Zykadia), crizotinib (Xalkori), nivolumab (Opdivo), and/or ramucirumab (Cyramza).
  • non-chemotherapeutic agents such as, for example, erlotinib (Tarceva), gefitinib, afatinib (Gilotrif), denosumab, bevacizumab (Avastin), ceritinib (Zykadia), crizotinib (Xalkori), nivolumab (Opdivo), and/or ramucirumab (Cyramza).
  • the present invention provides methods for the treatment of lung adenocarcinomas that comprise administration to a subject of one or more TNF-a inhibitors and also administration to the subject of one or more additional active agents selected from the group consisting of: Abitrexate (Methotrexate), Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation), Afatinib Dimaleate, Afinitor (Everolimus), Alecensa (Alectinib), Alectinib, Alimta (Pemetrexed Disodium), Avastin (Bevacizumab), Bevacizumab, Carboplatin, Ceritinib, Crizotinib, Cyramza (Ramucirumab), Docetaxel, Erlotinib Hydrochloride, Everolimus, Folex (Methotrexate), Folex PFS (Methotrexate), Gefitinib, Gilotrif (Afatinib Dimaleate),
  • additional active agents selected
  • Tax otere Docetaxel
  • Vinorelbine Tartrate Xalkori (Crizotinib)
  • Zykadia Ceritinib
  • the present invention provides methods for the treatment and/or prevention of lung adenocarcinoma in subjects in need thereof, such methods comprising administering to the subject an effective amount of certain active agents.
  • lung adenocarcinoma is used herein in accordance with its normal usage in the art and refers to a subtype of non-small cell lung cancers (NSCLCs).
  • NSCLCs non-small cell lung cancers
  • the terms “treat,” “treating,” and “treatment” encompass a variety of activities aimed at achieving a detectable improvement in one or more clinical indicators or symptoms associated with lung adenocarcinoma.
  • such terms include, but are not limited to, reducing the rate of growth of a lung cancer (or of lung cancer cells, or of other cells within a lung tumor), halting the growth of a lung cancer (or of lung cancer cells, or of other cells within a lung tumor), causing regression of a lung cancer (or of lung cancer cells, or of other cells within a lung tumor), reducing the size of a lung tumor (for example as measured in terms of tumor volume or tumor mass), reducing the grade of a lung cancer, eliminating a lung cancer (or lung cancer cells, or other cells within a lung tumor), preventing, delaying, or slowing recurrence (rebound) of a lung cancer, improving symptoms associated with lung cancer, improving survival from lung cancer, inhibiting or reducing spreading of a lung cancer (e
  • a lung adenocarcinoma is successfully prevented according to the methods provided herein if the patient develops, transiently or permanently, e.g., fewer or less severe symptoms associated with the lung adenocarcinoma, or a later onset of symptoms associated with the lung adenocarcinoma, than a patient who has not been subject to the methods and/or compositions of the invention.
  • the methods of treatment and/or prevention provided herein may be employed in conjunction with other lung adenocarcinoma treatment and/or prevention methods, including, but not limited to, surgical methods (e.g. for tumor resection), radiation therapy methods, treatment with chemotherapeutic agents, or treatment with non- chemotherapeutic agents.
  • the methods of treatment and/or prevention provided herein may be employed in conjunction with procedures used to monitor disease status/progression, such as biopsy methods and diagnostic methods (e.g. MRI methods or other imaging methods).
  • the present invention provides methods for determining whether a subject is a candidate for prevention or treatment using any of the compositions or methods provided herein. In some of such embodiments the subject is also subsequently treated using the compositions and/or methods provided herein.
  • the present invention provides methods for determining whether a subject is a candidate for treatment with a composition or method as described herein, wherein such methods involve performing an assay to determine if a subject has a lung adenocarcinoma having a S100A8/9 gene amplification, and/or if a subject has a lung adenocarcinoma in which S100A8/9 is over-expressed and/or over-produced, and/or if a subject has a lung adenocarcinoma in which T F- ⁇ is over-expressed and/or over-produced, and/or if a subject has a lung adenocarcinoma in which CXCLl/2 is over-expressed and/or over-produced.
  • Suitable assays that can be used are provided in the Examples section of this patent disclosure and/or are known in the art.
  • Each of the embodiments described herein that involves performing such an assay to determine whether a subject is a candidate for treatment may, in some embodiments, also comprise a preliminary step of obtaining a sample of lung adenocarcinoma cells from the subject, or obtaining a sample of protein, DNA, or RNA from such cells.
  • each of the embodiments described herein that involves performing an assay to determine whether a subject is a candidate for treatment may, in some embodiments, also comprise a subsequent step of treating the subject using one of the methods or compositions provided herein.
  • the methods of the present invention involve first determining whether a subject has a lung adenocarcinoma having a S100A8/9 gene amplification, and/or has a lung adenocarcinoma in which S100A8/9, T F- ⁇ , and/or CXCLl/2 is over-expressed and/or over-produced, and then, if the subject does have such a S100A8/9 gene amplification, and/or has a lung adenocarcinoma in which S100A8/9, TNF-a, and/or CXCLl/2 is over-expressed and/or overproduced, subsequently treating the subject with one of the methods or compositions described herein.
  • the terms "subject,” “individual,” and “patient” - which are used interchangeably herein, are intended to refer to any subject.
  • the subject is a mammalian subject. Mammalian subjects include humans, domestic animals, farm animals, sports animals, and zoo animals including, e.g., humans, non-human primates, dogs, cats, mice, rats, guinea pigs, and the like.
  • the subject is a human subject, for example a human subject for whom therapy or prophylaxis desired.
  • the subject has, or is suspected of having, a non-small cell lung cancer (NSCLC), such as, in particular, an adenocarcinoma of the lung.
  • NSCLC non-small cell lung cancer
  • the subject has an adenocarcinoma of the lung that is stage IA or above. In some embodiments the subject has an adenocarcinoma of the lung that is stage IB or above. In some embodiments the subject has an adenocarcinoma of the lung that is stage IIA or above. In some embodiments the subject has an adenocarcinoma of the lung that is stage IIB or above. In some embodiments the subject has an adenocarcinoma of the lung that is stage IIIA or above. In some embodiments the subject has an adenocarcinoma of the lung that is stage IIIB or above. In some embodiments the subject has an adenocarcinoma of the lung that is stage IV or above. [00040] In some embodiments the subject has an adenocarcinoma of the lung that is metastatic.
  • the subject has a lung adenocarcinoma having a S100A8/9 gene amplification. In some embodiments the subject has a lung adenocarcinoma in which S100A8/9 is over-expressed and/or over-produced. In some embodiments the subject has a lung adenocarcinoma in which T F- ⁇ is over-expressed and/or over-produced. In some embodiments the subject has a lung adenocarcinoma in which CXCLl/2 is over-expressed and/or over-produced.
  • any suitable method or route of administration can be used to deliver the active agents.
  • systemic administration means that the active agent is administered such that it enters the circulatory system, for example, via enteral, parenteral, inhalational, or transdermal routes.
  • Enteral routes of administration involve the gastrointestinal tract and include, without limitation, oral, sublingual, buccal, and rectal delivery.
  • Parenteral routes of administration involve routes other than the gastrointestinal tract and include, without limitation, intravenous,
  • intramuscular, intraperitoneal, intrathecal, and subcutaneous are intramuscular, intraperitoneal, intrathecal, and subcutaneous.
  • the TNF-a inhibitor antibody such as certolizumab
  • the TNF-a inhibitor antibody may be administered subcutaneously.
  • Local administration means that a pharmaceutical composition is administered directly to where its action is desired (e.g., at or near the site of a lung cancer), for example via direct intratumoral injection.
  • an effective amount refers to an amount of an active agent as described herein that is sufficient to achieve, or contribute towards achieving, one or more desirable clinical outcomes, such as those described in the "treatment” and “prevention” descriptions above.
  • An appropriate “effective” amount in any individual case may be determined using standard techniques known in the art, such as dose escalation studies, and may be determined taking into account such factors as the desired route of administration (e.g. systemic vs. local), the desired frequency of dosing, etc.
  • an "effective amount” may be determined in the context of any other active agents that are also to be used in the treatment method.
  • dosing studies may be performed using both the TNF-a inhibitor and the one or more additional active agents, because the effects of such agents may be synergistic.
  • One of skill in the art can readily perform such dosing studies to determine appropriate doses to use, for example using assays such as those described in the Examples section of this patent application and/or other assays known in the art.
  • Exemplary doses, dosing schedules, and routes of administration are provided herein, including in this Detailed Description and also in the Examples section of this patent disclosure. Furthermore, one of skill in the art will recognize that the various active agents described herein can be administered at other doses, and using other dosing schedules, and using other routes of administration. It is within the skill of the ordinary artisan to vary the exemplary doses, dosing schedules, and routes of administration provided herein, and to arrive at other suitable doses, suitable dosing schedules, and suitable routes of administration for any chosen active agent or combination of active agents.
  • the amount of any of the active agents described herein to be used for treatment may be may be about 100%, or about 90%, or about 80%, or about 70%, or about 60%, or about 50%, or about 40%, or about 30% of that agent's maximum tolerated dose in a subject.
  • the effective amount of the antibody to be administered systemically (e.g. subcutaneously) to a human subject may be about 100 mg, or about 150 mg, or about 200 mg, or about 250 mg, or about 300 mg, or about 350 mg, or about 400 mg, or about 450 mg, or about 500 mg, or about 550 mg, or about 600 mg, or about 650 mg, or about 700 mg, or about 750 mg, or about 800 mg, or more.
  • an effective amount of certolizumab to be administered systemically (e.g. subcutaneously) to a human subject may be about 100 mg - 500 mg. In some embodiments an effective amount of certolizumab to be administered systemically (e.g. subcutaneously) to a human subject may be about 200 mg - 400 mg. In some embodiments an effective amount of certolizumab to be administered systemically (e.g. subcutaneously) to a human subject may be about 200 mg. In some embodiments an effective amount of certolizumab to be administered systemically (e.g. subcutaneously) to a human subject may be about 400 mg.
  • the antibody may be administered systemically (e.g.
  • the T F- a inhibitor antibody certolizumab may be administered systemically (e.g. subcutaneously) to a human subject once every two weeks for a month and then monthly thereafter for as long as desired.
  • the antibody may be administered to a subject using any of the dosages, dosage schedules, or administration routes described in the April 2016 certolizumab pegol (Cimzia) prescribing information, the contents of which are hereby incorporated by reference.
  • the agents can be administered together (for example, in the same formulation and/or at the same time), or separately (for example, in different formulations and/or at different times). Where two or more active agents are used, it may be possible to use lower dosages or amounts of each active agent, as compared to the dosages necessary when each active agent is used alone.
  • the present invention provides compositions, for example pharmaceutical compositions.
  • pharmaceutical composition refers to a composition comprising at least one active agent as described herein, and one or more other components useful in formulating a composition for delivery to a subject, such as diluents, buffers, saline (such as phosphate buffered saline), cell culture media, carriers, stabilizers, dispersing agents, suspending agents, thickening agents, excipients, preservatives, and the like.
  • “Pharmaceutical compositions” permit the biological activity of the active agent, and do not contain components that are unacceptably toxic to the living subject to which the composition would be administered.
  • compositions can be in numerous dosage forms, for example, tablet, capsule, liquid, solution, soft-gel, suspension, emulsion, syrup, elixir, tincture, film, powder, hydrogel, ointment, paste, cream, lotion, gel, mousse, foam, lacquer, spray, aerosol, inhaler, nebulizer, ophthalmic drops, patch, suppository, and/or enema.
  • dosage forms and excipients will depends upon the active agent to be delivered and the specific disease or disorder to be treated or prevented, and can be selected by one of ordinary skill in the art without having to engage in any undue experimentation.
  • NCT02120807 was performed. The purpose of this study was to 1) establish the safety of the FDA-approved dose of certolizumab in conjunction with platinum-doublet chemotherapy and 2) determine whether the selected dose of certolizumab has the requisite in vivo pharmacodynamic effect of suppression of circulating TNF-a.
  • the primary endpoint was identification of a phase 2 dose (R2PD) by safety and pharmacodynamic criteria (suppression of TNF-a).
  • R2PD phase 2 dose
  • the median age of patients in the trial was 63 (42-71). 61% were female. 94% were former/current smokers.
  • the median KPS was 80%.
  • phase II Clinical Trial [00067] Having demonstrated adequate safety, promising efficacy, and a significant pharmacodynamic effect from treatment with certolizumab in a phase I clinical trial, phase II trials are conducted to determine if the addition of certolizumab to cisplatin + pemetrexed chemotherapy can improve the disease-free survival (DFS) of patients with stage IIIA lung adenocarcinomas by inhibiting the chemotherapy-induced paracrine inflammatory loop mediated by TNF-a that promotes the development of metastatic disease and chemotherapy resistance.
  • DFS disease-free survival
  • a single arm phase II design is employed.
  • Two previous studies of patients with stage IIIA lung adenocarcinomas are used as a historical control for determination of landmark DFS end-points (5, 6).
  • This trial addresses a critically important but understudied aspect of cancer treatment - the pathophysiology of metastatic propagation.
  • This treatment strategy can be paradigm- shifting - as such a strategy has not yet been employed in cancer therapy.
  • CXCL1 paracrine network links cancer chemoresi stance and metastasis.
  • Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457: 102-6.
  • Chemotherapy Is Prognostic of Survival in Patients With Stage IIIA pN2 Non-Small- Cell Lung Cancer: A Multicenter Phase II Trial. Journal of Clinical Oncology.

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Abstract

Dans certains modes de réalisation, la présente invention concerne des procédés utilisables dans le traitement de cancers du poumon, tels que l'adénocarcinome du poumon. Dans certains modes de réalisation, de tels procédés comprennent l'administration au patient le nécessitant d'un inhibiteur du TNF-a, tel que l'anticorps inhibiteur du TNF-a certolizumab, de façon optionnelle associé avec un ou plusieurs agents chimiothérapeutiques. Dans certains modes de réalisation, la présente invention concerne des compositions pharmaceutiques comprenant un inhibiteur du TNF-a et un ou plusieurs agents chimiothérapeutiques. Ces modes de réalisation, et d'autres, sont décrits plus en détail dans la présente demande de brevet.
PCT/US2017/033062 2016-05-17 2017-05-17 Traitement de l'adénocarcinome du poumon WO2017201142A1 (fr)

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