US20150216868A1 - Method of Adjuvant Cancer Treatment - Google Patents

Method of Adjuvant Cancer Treatment Download PDF

Info

Publication number
US20150216868A1
US20150216868A1 US14/422,182 US201314422182A US2015216868A1 US 20150216868 A1 US20150216868 A1 US 20150216868A1 US 201314422182 A US201314422182 A US 201314422182A US 2015216868 A1 US2015216868 A1 US 2015216868A1
Authority
US
United States
Prior art keywords
melanoma
dabrafenib
trametinib
treatment
amount
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US14/422,182
Other languages
English (en)
Inventor
Sylvie Laquerre
Peter F. Lebowitz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis Pharma AG
Novartis Pharmaceuticals Corp
Original Assignee
GlaxoSmithKline LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=50237545&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20150216868(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by GlaxoSmithKline LLC filed Critical GlaxoSmithKline LLC
Priority to US14/422,182 priority Critical patent/US20150216868A1/en
Assigned to GLAXOSMITHKLINE LLC reassignment GLAXOSMITHKLINE LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LAQUERRE, SYLVIE, LEBOWITZ, PETER F.
Assigned to GLAXOSMITHKLINE LLC reassignment GLAXOSMITHKLINE LLC CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE ADDRESS: 5 CRESCENT DR., PHILADELPHIA, PENNSYLVANIA 19112 PREVIOUSLY RECORDED ON REEL 031404 FRAME 0469. ASSIGNOR(S) HEREBY CONFIRMS THE CORPORATION SERVICE COMPANY, 2711 CENTERVILLE ROAD, SUITE 400, WILMINGTON, DELAWARE 19808. Assignors: GLAXOSMITHKLINE LLC
Assigned to NOVARTIS PHARMA AG reassignment NOVARTIS PHARMA AG ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GLAXO GROUP LIMITED
Assigned to GLAXO GROUP LIMITED reassignment GLAXO GROUP LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GLAXOSMITHKLINE LLC
Assigned to NOVARTIS AG reassignment NOVARTIS AG ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NOVARTIS PHARMA AG
Publication of US20150216868A1 publication Critical patent/US20150216868A1/en
Assigned to NOVARTIS PHARMACEUTICALS CORPORATION reassignment NOVARTIS PHARMACEUTICALS CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NOVARTIS AG
Abandoned legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • This invention relates to a method of treating subjects after complete resection of cutaneous melanoma.
  • Cutaneous melanoma is the most aggressive form of all skin cancers. Although it represents only 4% of all cancers, its incidence is continuing to rise in the world at a rate exceeding all other cancers (Jemal A, Siegel R, Ward E et al. Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43-66). Worldwide it is expected that approximately 132,000 people will be diagnosed with melanoma each year and approximately 37,000 people are expected to die of the disease annually (World Health Organization (WHO). Skin cancers. In Ultraviolet radiation and the INTERSUN Programme. Retrieved 7 Feb. 2012).
  • Surgical resection is the treatment of choice for localized melanoma and frequently results in cures for early stage (I and II) disease, with a 90% long term (10-year) survival rate for stage I disease Balch et al., Final Version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol. 2009; 27:6199-6206).
  • patients with lymph node involvement including those detected only by sentinel lymph node biopsy, are at high risk of both local and distant relapse after definitive surgery due to the frequent presence of distant micrometastatic disease at presentation (Kirkwood et al.
  • NCCN National Comprehensive Cancer Network
  • the present invention provides a method of providing adjuvant treatment to a patient with a prior diagnosis of melanoma which has been resected, which comprises administering to such a patient therapeutically effective doses of dabrafenib and trametinib for a time period sufficient to increase relapse-free survival (RFS).
  • RFS relapse-free survival
  • a method of increasing relapse-free survival (RFS) after resection of melanoma which comprises administration of a) dabrafenib and b) trametinib.
  • the patient has a prior diagnosis of stage III melanoma which primary tumor has been resected.
  • the patient has a prior diagnosis of BRAF V600 mutation-positive melanoma which has been resected.
  • the patient has stage III BRAF V600-mutation positive melanoma which has been resected,
  • the RAS/RAF/MEK/ERK pathway (i.e., the MAP kinase pathway) is a critical proliferation pathway in many human cancers, including melanoma. Oncogenic mutations in BRAF signal through MEK1 and MEK2, and occurrence of this is an early event.
  • Dabrafenib is a potent and selective RAF kinase inhibitor of human wild type BRAF and CRAF enzymes as well as the mutant forms BRAFV600E, BRAFV600K and BRAFV600D.
  • the mode of action of dabrafenib is consistent with competitive inhibition of adenosine triphosphate (ATP) binding.
  • trametinib is a reversible, highly selective, allosteric inhibitor of MEK1 and MEK2. Trametinib is non-competitive towards ATP and inhibits both MEK activation and kinase activity. Because BRAF and MEK are in the same pathway, and because MEK is a substrate of activated BRAF and other kinases that can be activated in presence of BRAF inhibition, inhibiting both proteins simultaneously rather than individually could provide more effective pathway inhibition and also decrease the likelihood of developing resistance.
  • dabrafenib as used herein means the B-Raf inhibitor represented by the structure of formula (II):
  • Dabrafenib is preferably administered as its mesylate salt as N- ⁇ 3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl ⁇ -2,6-difluorobenzenesulfonamide methanesulfonate.
  • Dabrafenib is disclosed and claimed, along with pharmaceutically acceptable salts thereof, as being useful as an inhibitor of BRaf activity, particularly in the treatment of cancer, in PCT patent publication WO2009/137391. Dabrafenib is embodied by Examples 58a through 58e of the application.
  • Dabrafenib is a potent and selective RAF kinase inhibitor of human wild type BRAF and CRAF enzymes as well as the mutant forms BRAFV600E, BRAFV600K and BRAFV600D. Accordingly, one embodiment of the invention includes adjuvant treatment of patients having BRAFV600E, BRAFV600K, and/or BRAFV600D mutation-positive melanoma which has been resected.
  • trametinib as used herein means the MEK inhibitor represented by the structure of formula (I):
  • Trametinib is preferably administered as a solvate in the form of N- ⁇ 3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl ⁇ acetamide dimethyl sulfoxide (solvate).
  • the compound of formula (I) may also properly be referred to as N- ⁇ 3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl ⁇ acetamide.
  • Trametinib is disclosed and claimed, along with pharmaceutically acceptable salts thereof, and also as solvates thereof, as being useful as an inhibitor of MEK activity, particularly in treatment of cancer, in WO 2005/121142.
  • Trametinib can be prepared as described in WO 2005/121142.
  • trametinib is in the form of a dimethyl sulfoxide solvate.
  • trametinib is in the form of a sodium salt.
  • trametinib is in the form of a solvate selected from: hydrate, acetic acid, ethanol, nitromethane, chlorobenzene, 1-pentancol, isopropyl alcohol, ethylene glycol and 3-methyl-1-butanol.
  • resection is understood to mean surgical removal of malignant tissue characteristic of melanoma from a human patient. According to one embodiment, resection shall be understood to mean removal of malignant tissue such that the presence of remaining malignant tissue within said patient is undetectable with available methods. According to another embodiment of the invention, resection shall be understood to mean removal of melanoma such that the presence of remaining melanoma with said patient is undetectable.
  • treatment or “adjuvant treatment” is understood to refer to the administration of a drug or drugs to a patient after surgical resection of one or more cancerous tumors, where all detectable and resectable disease (e.g. cancer) has been removed from the patient, but where there remains a statistical risk of relapse due to occult disease, for the purpose of diminishing the likelihood or the severity of reoccurrence or the disease, or to delay the onset of the biological manifestation of the reoccurrence of the disease.
  • all detectable and resectable disease e.g. cancer
  • the term “effective amount” means that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought, for instance, by a researcher or clinician.
  • therapeutically effective amount means any amount which, as compared to a corresponding subject who has not received such amount, results in improved treatment, healing, prevention, or amelioration of a disease, disorder, or side effect, or a decrease in the rate of advancement of a disease or disorder.
  • the term also includes within its scope amounts effective to enhance normal physiological function.
  • the invention further provides pharmaceutical compositions, which include dabrafenib and/or trametinib, and one or more pharmaceutically acceptable carriers, diluents, or excipients.
  • the carrier(s), diluent(s) or excipient(s) must be acceptable in the sense of being compatible with the other ingredients of the formulation, capable of pharmaceutical formulation, and not deleterious to the recipient thereof.
  • a process for the preparation of a pharmaceutical composition including admixing dabrafenib and/or trametinib, with one or more pharmaceutically acceptable carriers, diluents or excipients.
  • Such elements of the pharmaceutical compositions utilized may be presented in separate pharmaceutical combinations or formulated together in one pharmaceutical composition.
  • the invention further provides a combination of pharmaceutical compositions one of which includes trametinib and one or more pharmaceutically acceptable carriers, diluents, or excipients and a pharmaceutical composition containing dabrafenib and one or more pharmaceutically acceptable carriers, diluents, or excipients.
  • Dabrafenib and/or trametinib may be administered by any appropriate route. Suitable routes include oral, rectal, nasal, topical (including buccal and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intraveneous, intradermal, intrathecal, and epidural). It will be appreciated that the preferred route may vary with, for example, the condition of the recipient of the combination and the cancer to be treated. It will also be appreciated that each of the agents administered may be administered by the same or different routes and that the compounds may be compounded together in a pharmaceutical composition.
  • Dabrafenib and trametinib may be employed in combination in accordance with the invention by administration simultaneously in a unitary pharmaceutical composition including both compounds.
  • the combination may be administered separately in separate pharmaceutical compositions, each including one of the dabrafenib and trametinib in a sequential manner wherein, for example, trametinib or dabrafenib is administered first and the other second.
  • Such sequential administration may be close in time (e.g. simultaneously) or remote in time.
  • the compounds are administered in the same dosage form, e.g. one compound may be administered topically and the other compound may be administered orally.
  • both compounds are administered orally.
  • one or more doses of trametinib are administered simultaneously or separately with one or more doses of dabrafenib.
  • the amount of trametinib (based on weight of unsalted/unsolvated amount) administered as part of the combination according to the present invention will be an amount selected from about 0.125 mg to about 10 mg; suitably, the amount will be selected from about 0.25 mg to about 9 mg; suitably, the amount will be selected from about 0.25 mg to about 8 mg; suitably, the amount will be selected from about 0.5 mg to about 8 mg; suitably, the amount will be selected from about 0.5 mg to about 7 mg; suitably, the amount will be selected from about 1 mg to about 7 mg; suitably, the amount will be about 5 mg. Accordingly, the amount of trametinib administered as part of the combination according to the present invention will be an amount selected from about 0.125 mg to about 10 mg.
  • the amount of trametinib administered as part of the combination according to the present invention can be 0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg.
  • the amount of dabrafenib (based on weight of unsalted/unsolvated amount) administered as part of the combination according to the present invention will be an amount selected from about 10 mg to about 600 mg.
  • the amount will be selected from about 30 mg to about 300 mg; suitably, the amount will be selected from about 30 mg to about 280 mg; suitably, the amount will be selected from about 40 mg to about 260 mg; suitably, the amount will be selected from about 60 mg to about 240 mg; suitably, the amount will be selected from about 80 mg to about 220 mg; suitably, the amount will be selected from about 90 mg to about 210 mg; suitably, the amount will be selected from about 100 mg to about 200 mg, suitably, the amount will be selected from about 110 mg to about 190 mg, suitably, the amount will be selected from about 120 mg to about 180 mg, suitably, the amount will be selected from about 130 mg to about 170 mg, suitably, the amount will be selected from about 140 mg to about 160 mg, suitably, the amount will be 150
  • the amount of dabrafenib administered as part of the combination according to the present invention will be an amount selected from about 10 mg to about 300 mg.
  • the amount of dabrafenib administered as part of the combination according to the present invention is suitably selected from 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 195 mg, 200 mg, 205 mg, 210 mg, 215 mg, 220 mg, 225 mg, 230 mg, 235 mg, 240 mg, 245 mg, 250 mg, 255 mg, 260 mg, 265 mg, 270 mg, 275 mg, 280 mg, 285 mg, 290 mg, 295 mg and 300 mg.
  • the selected amount of dabrafenib is administered from 1 to 4 times a day.
  • the selected amount of dabrafenib is administered twice a day.
  • dabrafenib is administered at an amount of 150 mg twice a day.
  • the selected amount of dabrafenib is administered once a day.
  • the combination of the invention may be employed with other therapeutic methods of cancer treatment.
  • combination therapy with other chemotherapeutic, hormonal, antibody agents as well as surgical and/or radiation treatments other than those mentioned above are envisaged.
  • Combination therapies according to the present invention thus include the administration of trametinib and dabrafenib as well as optional use of other therapeutic agents including other anti-neoplastic agents.
  • Such combination of agents may be administered together or separately and, when administered separately this may occur simultaneously or sequentially in any order, both close and remote in time.
  • the pharmaceutical combination includes trametinib and dabrafenib, and optionally at least one additional anti-neoplastic agent.
  • Cutaneous melanoma is the most aggressive form of all skin cancers. Although it represents only 4% of all cancers, its incidence is continuing to rise in the world at a rate exceeding all other cancers [Jemal, 2007]. Worldwide it is expected that approximately 132,000 people will be diagnosed with melanoma each year and approximately 37,000 people are expected to die of the disease annually [WHO, 2012].
  • Surgical resection is the treatment of choice for localized melanoma and frequently results in cures for early stage (I and II) disease, with a 90% long term (10-year) survival rate for stage I disease [Balch, 2009].
  • patients with lymph node involvement ⁇ 1 mm, including those detected only by sentinel lymph node biopsy, are at high risk of both local and distant relapse after definitive surgery due to the frequent presence of distant micrometastatic disease at presentation [Kirkwood, 2001; Van Akkooi, 2009].
  • Approximately half of these patients will ultimately die of metastatic disease [Markovic, 2007], and the morbidity from uncontrolled relapses is also considerable.
  • NCCN National Comprehensive Cancer Network
  • Doses of study treatment may be modified and/or interrupted for management of toxicities associated with study treatment.
  • Subjects in both arms will receive treatment for 12 months or until disease recurrence, death, unacceptable toxicity, or withdrawal of consent. Subjects will be followed for disease recurrence and survival during and after the treatment period.
  • the primary objective for this study is to evaluate the efficacy of dabrafenib and trametinib combination therapy compared to two placebos with respect to relapse-free survival (RFS) in patients with completely resected, histologically confirmed, BRAF V600E/K high-risk, stage III cutaneous melanoma.
  • Secondary efficacy objectives include:
  • the ultimate goal of adjuvant therapy is to improve the cure rate after surgery through eradication of occult micrometastatic disease. Notable successes have been achieved in oncology when highly effective therapies were available for advanced stage disease (e.g., breast cancer, Hodgkin's and non-Hodgkin's lymphoma, embryonal tumors, osteosarcoma).
  • advanced stage disease e.g., breast cancer, Hodgkin's and non-Hodgkin's lymphoma, embryonal tumors, osteosarcoma.
  • High-risk, resected BRAF V600E/K mutation positive melanoma represents another attractive setting for testing this paradigm since: 1) the population is at high risk for relapse and death without further therapy; 2) the BRAF/MEK combination is both highly effective and can be targeted to the population most likely to benefit, and 3) the combination of dabrafenib and trametinib should be at least as well tolerated as cytotoxic chemotherapy or high-dose interferon and thus have acceptable risk:benefit if the study objectives are met.
  • RFS is a direct measurement of anti-tumor effect.
  • RFS was selected as the primary endpoint based upon historical precedent (peginterferon alfa-2b, Sylatron) and because it will not be subject to confounding from subsequent therapy, as would OS. Since relapses are accompanied by considerable disease- and treatment-related morbidity, RFS is a true measure of patient benefit.
  • study treatment(s) may be permanently discontinued for the following reasons:
  • a subject will be considered to have completed the study if the subject dies during the study treatment or follow-up period.
  • a subject will be considered to have withdrawn from the study if the subject has not died and is lost to follow-up, has withdrawn consent, at the investigator's discretion is no longer being followed or if the study is closed/terminated. Subjects who are ongoing at the time the study is closed/terminated will be considered to have completed the study.
  • Subjects will be assessed with computed tomography (CT) or magnetic resonance imaging (MRI) at Screening and during treatment and the post-treatment follow-up period.
  • CT computed tomography
  • MRI magnetic resonance imaging
  • Clinical assessments including vital signs and physical examinations, 12-lead ECG, ECHO, eye exams, chemistry and hematology laboratory values, and AEs will be monitored and evaluated. Subjects will also be followed for survival.
  • Subjects will be identified by a unique subject number that will remain consistent for the duration of the study.
  • IVRS GSK interactive voice response system
  • Randomization will be done centrally using a randomization schedule generated by the GSK Biostatistical Department, which will assign subjects in a 1:1 ratio to:
  • NCI National Cancer Institute
  • the primary efficacy endpoint of this study is relapse free survival (RFS) which is defined as the time from randomization to disease recurrence or death from any cause. Recurrence of or death from the same cancer and all deaths from other causes are events. Treatment emergent malignancies (excluding second melanomas) will not be considered as events, and loss to follow-up is censored.
  • RFS relapse free survival

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Steroid Compounds (AREA)
US14/422,182 2012-09-04 2013-08-30 Method of Adjuvant Cancer Treatment Abandoned US20150216868A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/422,182 US20150216868A1 (en) 2012-09-04 2013-08-30 Method of Adjuvant Cancer Treatment

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261696375P 2012-09-04 2012-09-04
PCT/US2013/057432 WO2014039375A1 (en) 2012-09-04 2013-08-30 Method of adjuvant cancer treatment
US14/422,182 US20150216868A1 (en) 2012-09-04 2013-08-30 Method of Adjuvant Cancer Treatment

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/057432 A-371-Of-International WO2014039375A1 (en) 2012-09-04 2013-08-30 Method of adjuvant cancer treatment

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/479,663 Continuation US20170202842A1 (en) 2012-09-04 2017-04-05 Method of Adjuvant Cancer Treatment

Publications (1)

Publication Number Publication Date
US20150216868A1 true US20150216868A1 (en) 2015-08-06

Family

ID=50237545

Family Applications (6)

Application Number Title Priority Date Filing Date
US14/422,182 Abandoned US20150216868A1 (en) 2012-09-04 2013-08-30 Method of Adjuvant Cancer Treatment
US15/479,663 Abandoned US20170202842A1 (en) 2012-09-04 2017-04-05 Method of Adjuvant Cancer Treatment
US16/056,702 Abandoned US20180338979A1 (en) 2012-09-04 2018-08-07 Method of Adjuvant Cancer Treatment
US16/664,978 Active US10869869B2 (en) 2012-09-04 2019-10-28 Method of adjuvant cancer treatment
US17/095,200 Abandoned US20210060021A1 (en) 2012-09-04 2020-11-11 Method of Adjuvant Cancer Treatment
US18/062,764 Pending US20230330091A1 (en) 2012-09-04 2022-12-07 Method of Adjuvant Cancer Treatment

Family Applications After (5)

Application Number Title Priority Date Filing Date
US15/479,663 Abandoned US20170202842A1 (en) 2012-09-04 2017-04-05 Method of Adjuvant Cancer Treatment
US16/056,702 Abandoned US20180338979A1 (en) 2012-09-04 2018-08-07 Method of Adjuvant Cancer Treatment
US16/664,978 Active US10869869B2 (en) 2012-09-04 2019-10-28 Method of adjuvant cancer treatment
US17/095,200 Abandoned US20210060021A1 (en) 2012-09-04 2020-11-11 Method of Adjuvant Cancer Treatment
US18/062,764 Pending US20230330091A1 (en) 2012-09-04 2022-12-07 Method of Adjuvant Cancer Treatment

Country Status (21)

Country Link
US (6) US20150216868A1 (zh)
EP (2) EP3981408A1 (zh)
JP (3) JP2015527374A (zh)
KR (1) KR102134585B1 (zh)
CN (2) CN107308164A (zh)
AU (2) AU2013313050A1 (zh)
BR (1) BR112015004578A2 (zh)
CA (1) CA2882437C (zh)
CY (1) CY1124812T1 (zh)
DK (1) DK2892535T3 (zh)
ES (1) ES2900825T3 (zh)
HK (1) HK1206642A1 (zh)
HR (1) HRP20211817T1 (zh)
HU (1) HUE056646T2 (zh)
IN (1) IN2015KN00449A (zh)
LT (1) LT2892535T (zh)
PL (1) PL2892535T3 (zh)
PT (1) PT2892535T (zh)
RU (1) RU2640180C2 (zh)
SI (1) SI2892535T1 (zh)
WO (1) WO2014039375A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11266653B2 (en) 2017-05-02 2022-03-08 Novartis Ag Combination therapy
US12011449B2 (en) 2016-09-19 2024-06-18 Novartis Ag Therapeutic combinations comprising a c-RAF inhibitor

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2892535T3 (pl) 2012-09-04 2022-01-31 Novartis Ag Sposób leczenia adjuwantowego raka
EP3087204B1 (en) 2013-12-28 2018-02-14 Guardant Health, Inc. Methods and systems for detecting genetic variants
WO2019204399A1 (en) * 2018-04-17 2019-10-24 The University Of Chicago Methods and compositions for treating cancer
CN109106893B (zh) * 2018-11-12 2021-04-20 上海市中西医结合医院 一种调节肠道屏障功能的中药复方制剂及其制备方法
CN118767143A (zh) * 2019-12-12 2024-10-15 听治疗有限责任公司 用于预防和治疗听力损失的组合物和方法
WO2023105286A1 (en) 2021-12-06 2023-06-15 My Personal Therapeutics Ltd A combination treatment for cancer

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011047238A1 (en) * 2009-10-16 2011-04-21 Glaxosmithkline Llc Combination

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2397825T3 (es) * 2004-06-11 2013-03-11 Japan Tobacco, Inc. Derivados de 5-amino-2,4,7-trioxo-3,4,7,8-tetrahidro-2H-pirido[2,3-d]pirimidina y compuestos relacionados para el tratamiento del cáncer
CA3054535A1 (en) * 2005-02-18 2006-08-24 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
UA103319C2 (en) * 2008-05-06 2013-10-10 Глаксосмитклайн Ллк Thiazole- and oxazole-benzene sulfonamide compounds
US20130004481A1 (en) * 2011-01-12 2013-01-03 Boehringer Ingelheim International Gmbh Anticancer therapy
PL2892535T3 (pl) 2012-09-04 2022-01-31 Novartis Ag Sposób leczenia adjuwantowego raka

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011047238A1 (en) * 2009-10-16 2011-04-21 Glaxosmithkline Llc Combination

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Atefi et al., PLoS ONE, 2011;6(12):e28973 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12011449B2 (en) 2016-09-19 2024-06-18 Novartis Ag Therapeutic combinations comprising a c-RAF inhibitor
US11266653B2 (en) 2017-05-02 2022-03-08 Novartis Ag Combination therapy
US12036227B2 (en) 2017-05-02 2024-07-16 Novartis Ag Combination therapy

Also Published As

Publication number Publication date
AU2016244279B2 (en) 2018-01-04
CN104582706A (zh) 2015-04-29
RU2640180C2 (ru) 2017-12-26
EP3981408A1 (en) 2022-04-13
PT2892535T (pt) 2021-12-15
WO2014039375A1 (en) 2014-03-13
ES2900825T3 (es) 2022-03-18
SI2892535T1 (sl) 2022-01-31
JP2018058859A (ja) 2018-04-12
HK1206642A1 (zh) 2016-01-15
PL2892535T3 (pl) 2022-01-31
CA2882437A1 (en) 2014-03-13
US20210060021A1 (en) 2021-03-04
AU2016244279A1 (en) 2016-11-03
US20230330091A1 (en) 2023-10-19
US20170202842A1 (en) 2017-07-20
US10869869B2 (en) 2020-12-22
CN107308164A (zh) 2017-11-03
US20200054641A1 (en) 2020-02-20
LT2892535T (lt) 2021-12-10
RU2015105821A (ru) 2016-10-20
BR112015004578A2 (pt) 2017-07-04
DK2892535T3 (da) 2022-01-03
IN2015KN00449A (zh) 2015-07-17
JP6684941B2 (ja) 2020-04-22
CY1124812T1 (el) 2022-11-25
JP2019142899A (ja) 2019-08-29
KR102134585B1 (ko) 2020-07-17
KR20150047619A (ko) 2015-05-04
CA2882437C (en) 2021-03-02
EP2892535A1 (en) 2015-07-15
JP6511117B2 (ja) 2019-05-15
US20180338979A1 (en) 2018-11-29
HUE056646T2 (hu) 2022-02-28
AU2013313050A1 (en) 2015-03-26
HRP20211817T1 (hr) 2022-03-04
JP2015527374A (ja) 2015-09-17
EP2892535B1 (en) 2021-09-22
EP2892535A4 (en) 2016-04-13

Similar Documents

Publication Publication Date Title
US10869869B2 (en) Method of adjuvant cancer treatment
Xia et al. Repurposing of antipsychotic trifluoperazine for treating brain metastasis, lung metastasis and bone metastasis of melanoma by disrupting autophagy flux
TW201919615A (zh) 用於治療tnbc的化合物
CA3240993A1 (en) Cdk4 inhibitor for the treatment of cancer
US20170112865A1 (en) Treatment for melanoma
JP7278405B2 (ja) 小細胞肺がんの治療におけるキアウラニブの使用
US20210205272A1 (en) Dosing regimens for treatment of solid tumors having one or more genetic alterations in fgfr1, fgfr2, and/or fgfr3
TW202329946A (zh) 用於治療癌症之方法及包含cdk2抑制劑之給藥方案
WO2021104341A1 (zh) 一种取代丁烯酰胺的应用
KR20150003786A (ko) Pi3k 저해제 및 mek 저해제를 이용한 암 치료 방법
US20220073642A1 (en) Methods of using surufatinib in treating advanced pancreatic and extra-pancreatic neuroendocrine tumors
WO2017030146A1 (ja) 胆道癌治療剤
US20190134003A1 (en) Combination therapies using indazolylbenzamide derivatives for the treatment of cancer
Schilder et al. An Open-Label Study to Determine the Maximum Tolerated Dose of Oral ESK-440 Administered as a Single Agent in Patients with Advanced or Metastatic Solid Tumors

Legal Events

Date Code Title Description
AS Assignment

Owner name: GLAXOSMITHKLINE LLC, PENNSYLVANIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LAQUERRE, SYLVIE;LEBOWITZ, PETER F.;REEL/FRAME:031404/0469

Effective date: 20130913

AS Assignment

Owner name: GLAXOSMITHKLINE LLC, DELAWARE

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE ADDRESS: 5 CRESCENT DR., PHILADELPHIA, PENNSYLVANIA 19112 PREVIOUSLY RECORDED ON REEL 031404 FRAME 0469. ASSIGNOR(S) HEREBY CONFIRMS THE CORPORATION SERVICE COMPANY, 2711 CENTERVILLE ROAD, SUITE 400, WILMINGTON, DELAWARE 19808;ASSIGNOR:GLAXOSMITHKLINE LLC;REEL/FRAME:035048/0656

Effective date: 20140509

AS Assignment

Owner name: GLAXO GROUP LIMITED, ENGLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GLAXOSMITHKLINE LLC;REEL/FRAME:035806/0320

Effective date: 20150301

Owner name: NOVARTIS PHARMA AG, SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GLAXO GROUP LIMITED;REEL/FRAME:035806/0563

Effective date: 20150302

AS Assignment

Owner name: NOVARTIS AG, SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NOVARTIS PHARMA AG;REEL/FRAME:035812/0424

Effective date: 20150302

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: NOVARTIS PHARMACEUTICALS CORPORATION, NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:NOVARTIS AG;REEL/FRAME:065762/0911

Effective date: 20231204