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WO2018144334A1 - Schéma posologique pour anticorps anti-csf-1r - Google Patents

Schéma posologique pour anticorps anti-csf-1r Download PDF

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Publication number
WO2018144334A1
WO2018144334A1 PCT/US2018/015412 US2018015412W WO2018144334A1 WO 2018144334 A1 WO2018144334 A1 WO 2018144334A1 US 2018015412 W US2018015412 W US 2018015412W WO 2018144334 A1 WO2018144334 A1 WO 2018144334A1
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WIPO (PCT)
Prior art keywords
antibody
dose
once
cancer
week
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Application number
PCT/US2018/015412
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English (en)
Inventor
Sae Wook KAUH
Original Assignee
Imclone Llc
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Publication of WO2018144334A1 publication Critical patent/WO2018144334A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule

Definitions

  • This invention is directed to the fields of immunology and cancer treatment. More specifically, the present invention is directed to the dosing of the anti-Colony Stimulating Factor-1 Receptor (CSF-IR) antibody, Antibody 1, as a medicament for the treatment of cancer. More specifically the present invention is directed to the dosing Antibody 1 at a dose of about 100 mg once a week or about 100 mg of Antibody 1 once every two weeks.
  • CSF-IR Colony Stimulating Factor-1 Receptor
  • the present invention is directed to the treatment of cancer where the cancer includes but are not limited to breast (including but not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression), ovarian (including but not limited to fallopian tube, primary peritoneal, and epithelia), melanoma, and lung (including but not limited to non- small cell).
  • breast including but not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression
  • ovarian including but not limited to fallopian tube, primary peritoneal, and epithelia
  • melanoma including but not limited to non- small cell.
  • Macrophages are among the immune cells that infiltrate solid tumors. In many cancers, higher levels of macrophage infiltration have been associated with poorer prognosis. Ruffell & Coussens, Cancer Cell (2015) 27 (4):462. Tumor-associated macrophages (TAM) are abundant in tumors, and promote growth, angiogenesis, and metastasis through secretion of proangiogenic factors and remodeling of the tumor stroma. In addition, TAMs are known to cause suppression of anticancer immune responses through direct inhibition of anti-tumor T cells by production of reactive oxygen species and suppressive cytokines. Id.
  • TAM Tumor-associated macrophages
  • CSF-IR also known as M-CSFR or CD-I 15
  • M-CSFR a tyrosine kinase receptor expressed selectively on monocytes/macrophage and granulocyte cell lineages in normal individuals and on tumor cells in cancer.
  • CSF-IR dimerizes, leading to trans-phosphorylation of the receptor and phosphorylation and activation of downstream signaling molecules such as MAPK and Akt.
  • CSF-IR results in: (1) the proliferation and differentiation of macrophages from hematopoietic progenitor stem cells, (2) survival and migration of macrophages to various organs and tissues in the body, particularly the tumor stroma, and (3) maintenance of the immune suppressive phenotype of TAM and other CSF-IR expressing cells of the myeloid lineage.
  • CSF-IR inhibition Given the critical role of CSF-IR in the regulation and survival of TAMs and other myeloid cells, CSF-IR inhibition has been identified as a potential cancer target.
  • the present invention seeks to provide a method of administering Antibody 1, a CSF-IR antibody, in response to a clinically unmet need for patients who fail to respond to typical therapeutic antibody dosing regimens and/or experience adverse events or toxicity issues with the typical therapeutic antibody dosing regimens.
  • the Antibody 1 dosing regimen of the present invention provides a solution to an unmet need for patients who fail to respond the standard dosing regimens of Antibody 1.
  • Antibody 1 is a recombinant human monoclonal antibody that specifically targets the human CSF-IR.
  • the amino acid sequences of the light chains and heavy chains of Antibody 1 are disclosed in WO2011/123381 Al and in US Patent No. 8,263,079.
  • WO2011/123381 and US Patent No. 8,263,079 also disclose the treatment of a variety of neoplastic diseases, including leukemia, breast cancer, endometrial cancer, prostate cancer, ovarian cancer, colorectal cancer, hepatocellular cancer, renal cancer, multiple myeloma, and Hodgkin's lymphoma with Antibody 1.
  • Antibody 1 also known as JJVIC-CS4 and LY3022855
  • JSCB NCT02265536
  • JSCC NCT02718911
  • WO2011/123381 discloses broad dosing ranges for Antibody 1 which is typical for therapeutic monoclonal antibodies: "An exemplary, non-limiting range for a therapeutically effective amount of Antibody 1 is 0.1-50 mg/kg, more preferably 3-35 mg/kg, and more preferably 5-20 mg/kg. Dosing amounts and frequencies will be determined by the physician treating the patient and may include doses from less than 1 mg/kg to over 100 mg/kg given daily, three times per week, weekly, once every two weeks, or less often.” Page 20, lines 14-19.
  • Dosing is an added complexity that drives further unpredictability. Not all drug dosing regimens are equally suitable for a particular therapy due to various factors, including but not limited to, body weight, performance status, number of prior systemic therapies, genetics, and histological tumor type. Toxicity issues introduce additional complexities. Efficacy and toxicity must be balanced.
  • the dosing regimen of the present invention is effective, from a pharmacokinetic (PK) / pharmacodynamics (PD) perspective, despite being a non-weight based therapeutic regimen.
  • PK pharmacokinetic
  • PD pharmacodynamics
  • Higher doses proved to have toxicology issues, and lower doses failed to provide consistent blockade of the CSF-1R signaling pathway, as demonstrated by persistent elevation of circulating CSF-1 levels, as well as suppression of circulating non- classical/inflammatory monocytes required to enable a therapeutic effect.
  • the claimed dosing regimens provide the required balance.
  • the proposed starting dose and regimen of Antibody 1 in the original dose escalation study for Antibody 1, JSCA was 2.5 mg/kg, administered weekly by intravenous infusion.
  • JSCA was originally designed to administer to various patient cohorts doses of 2.5, 5, 10, 20, and 40 mg/kg Antibody 1 once every week (hereinafter "QW") respectively, however as discussed herein, based upon observed toxicology considerations, JSCA was modified to significantly lower the dosing in subsequent cohorts from 2.5 mg/kg (QW) and up, to 0.3 mg/kg (QW), 0.6 mg/kg (QW), 1.25 mg/kg (every two weeks, hereinafter "Q2W”), and 1.25 mg/kg (QW) such that the highest dose was half of the original proposed starting dose.
  • QW doses of 2.5, 5, 10, 20, and 40 mg/kg Antibody 1 once every week
  • the recommended phase 2 dose for AMG820 is likely 6 mg/kg and accordingly, if one assumes a 80 kg patient, the dose is 480 mg every two weeks, which will result in a 240% higher exposure than the dose regimen of the present invention.
  • These ranges are weight-based and are significantly higher than the dosing regimen of the presently claimed invention.
  • Antibody 1 for use in the treatment of cancer, wherein Antibody 1 is administered at a dose of about 100 mg once a week or at a dose of about 100 mg once every two weeks. In another aspect of the invention, Antibody 1 is administered at a dose of about 100 mg once a week. In another aspect of the invention, Antibody 1 is administered at a dose of about 100 mg once every two weeks.
  • the cancer is breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • Antibody 1 for the preparation of a medicament for the treatment of cancer wherein Antibody 1 is administered at a dose of about 100 mg once a week or at a dose of about 100 mg once every two weeks. In another aspect of the invention, Antibody 1 is administered at a dose of about 100 mg once a week. In another aspect of the invention, Antibody 1 is administered at a dose of about 100 mg once every two weeks.
  • the cancer is breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • a medicament comprising Antibody 1, wherein the Antibody 1 is administered at a dose of about 100 mg once a week or about 100 mg of Antibody 1 once every two weeks.
  • the medicament is for use in the treatment of breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • a pharmaceutical composition comprising Antibody 1, wherein to a patient, the Antibody 1 is administered at a dose of about 100 mg once a week or about 100 mg of Antibody 1 once every two weeks.
  • the pharmaceutical composition is for use in the treatment of breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • kits comprising a pharmaceutical composition comprising Antibody 1 with one or more pharmaceutically acceptable carriers, diluents, or excipients wherein the Antibody 1 is administered at a dose of about 100 mg once a week or about 100 mg of Antibody 1 once every two weeks.
  • the kit is used for the treatment of breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • a method of administering an effective amount of Antibody 1 to a patient in need thereof comprising administering a dose of about 100 mg of Antibody 1 once a week or about 100 mg of Antibody 1 once every two weeks.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once a week.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once every two weeks.
  • the patient has breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • a therapeutic regimen for Antibody 1 in the treatment of cancer comprising about 100 mg of Antibody 1 administered once a week or about 100 mg of Antibody 1 once every two weeks.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once a week.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once every two weeks.
  • the cancer is breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • a method of reducing the risk of disease progression of a patient having cancer comprising administering about 100 mg of Antibody 1 once a week or about 100 mg of Antibody 1 once every two weeks.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once a week.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once every two weeks.
  • the cancer is breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • a method of treating cancer in a patient in need thereof comprising administering about 100 mg of Antibody 1 once a week or about 100 mg of Antibody 1 once every two weeks.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once a week.
  • Antibody 1 is administered at a dose of about 100 mg of Antibody 1 once every two weeks.
  • the cancer is breast cancer, ovarian cancer, melanoma, or lung cancer.
  • the breast cancer includes but is not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression breast cancer.
  • the ovarian cancer includes but is not limited to fallopian tube, primary peritoneal, and epithelia ovarian cancer.
  • the lung cancer includes but is not limited to non-small cell lung cancer.
  • Antibody 1 refers to an anti-CSF-lR antibody comprising: two heavy chains, each of whose amino acid sequence is that is given in SEQ ID NO: 3, and two light chains, each of whose amino acid sequences is given in SEQ ID NO: 4.
  • treating refers to restraining, slowing, lessening, reducing, or reversing the progression or severity of an existing symptom, disorder, condition, or disease or ameliorating clinical symptoms of a condition.
  • beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of the extent of a disease or disorder, stabilization of a disease or disorder (i.e., where the disease or disorder does not worsen), delay or slowing of the progression of a disease or disorder, amelioration or palliation of the disease or disorder, and remission (whether partial or total) of the disease or disorder, whether detectable or undetectable.
  • Treatment can also mean prolonging survival as compared to expected survival if not receiving treatment. Those in need of treatment include those already with the disease.
  • the present invention can be used as a medicament.
  • cancer and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Included in this definition are benign and malignant cancers.
  • human antibodies of the invention are particularly suitable for administration to humans, they can be administered to other mammals as well. Accordingly, as used herein, the term "patient” refers to a mammal, preferably a human.
  • the term mammal as used herein is intended to include, but is not limited to, humans, laboratory animals, domestic pets, and farm animals.
  • a “therapeutically effective amount” or “effective amount” as used herein, refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result.
  • a therapeutically effective amount is also one in which any toxic or detrimental effects of the antibody or antibody portion are outweighed by the therapeutically beneficial effects.
  • an "unexpected therapeutic effect" of the treatment of the invention is the ability to produce marked anti-cancer effects in a patient, so that the patient benefits from the treatment overall.
  • the efficacy, i.e., therapeutic effect(s), of the treatment of the invention can be measured by various endpoints commonly used in evaluating cancer treatments, include any one or more including, but not limited to: extending survival (including overall survival (OS) and progression free survival (PFS)); resulting in an objective response (including a complete response (CR) or a partial response (PR)); tumor regression, tumor weight or size shrinkage; longer time to disease progression; increased duration of survival; longer PFS; improved OS rate; increased duration of response; and improved quality of life and/or improving signs or symptoms of cancer, etc.
  • Novel approaches to determine efficacy, i.e., therapeutic effect(s), of the present invention can be optionally employed, including, for example, measurement of plasma, serum, or urinary markers and measurement of response through radiological imaging.
  • AE reverse event
  • DLTs dose-limiting toxicities
  • Grade 3 or 4 nonhematologic AEs DLT exceptions include: Grade >3 liver function test (LFT) abnormality, such as alkaline phosphatase, gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), without evidence of hepatic injury; transient Grade >2 bilirubin elevation in the presence of known liver metastases lasting ⁇ 7 days; laboratory abnormalities that are reversible to Grade ⁇ 2 or baseline levels within 7 days after initial documentation or that are deemed not clinically significant; and Grade 3 elevation of CK without elevation in serum and urine myoglobin.
  • LFT liver function test
  • GTT gamma glutamyl transferase
  • AST aspartate aminotransferase
  • ALT alanine aminotransferase
  • any suitable method or route can be used to administer Antibody 1, and optionally, to co-administer anti -neoplastic agents and/or antagonists of other receptors.
  • Antibody 1 where used in a mammal for the purpose of treatment, is preferably formulated as pharmaceutical compositions.
  • Such pharmaceutical compositions and processes for preparing the same are well known in the art. See, e.g. Remington: The Science and Practice of Pharmacy, L.V. Allen, Editor, 22 nd Edition, Pharmaceutical Press, 2012.
  • Antibody 1 is preferably formulated as pharmaceutical compositions administered by a route that makes the compound bioavailable.
  • Antibody 1 compositions are for parenteral administration, such as intravenous (i.v.) administration.
  • Such pharmaceutical compositions and processes for preparing same are well known in the art. ⁇ See e.g., id).
  • CK creatatine kinase
  • myoglobin level means the concentration of myoglobin found in bodily fluids including urine and blood serum.
  • myoglobins can be measured by a standardized immunochemiluminometric assay (ICMA).
  • ICMA immunochemiluminometric assay
  • serum myoglobin's can be measured by a standardized eletrochemiluminescence immunoassay (ECLIA) or enzyme-linked immunosorbent assay (ELISA).
  • CSF-1 is the ligand to CSF-1R.
  • circulating CSF-1 means the quantity of ligand in the blood. Circulating CSF-1 can be measured by ELISA.
  • CD14 Dim CD16 Bri ht cells mean the concentration of white blood cells in peripheral blood which express cell surface markers, including but not limited to CD45 (protein tyrosine phosphatase, receptor type c) and ULA-DR (Human leukocyte antigen, antigen D related), and which have low expression of CD 14 (Myeloid Cell-Specific Leucine-Rich Glycoprotein), and highest expression of CD 16 (Fc gamma receptor III) as measured by Fluorescence-activated cell sorting (FACS).
  • the CD16 Bnght population is determined as the highest level of measureable expression as measured by FACS.
  • the CD14 Dim population is determined as those cells expressing CD14, lower than the brightest CD 14 positive population, but higher in expression than negative controls.
  • CD14 Bnght population is determined as the cells which express the highest measurable level of CD 14, but express no CD 16.
  • Antibody 1 can be made, for example, according to the disclosure in WO2011/123381.
  • JSCA Phase 1 Study of Antibody 1, a Monoclonal Antibody Targeted to the CSF-1 Receptor (CSF-1R), In Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy is Available", NCT01346358)
  • the primary objectives are to establish the safety profile and characterize the PK profile of Antibody 1 in the treatment of subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy is available.
  • the secondary objectives are: (1) Part A only: To define the recommended Phase 2 dose using weight-based dosing; (2) Part B only: To define the recommended Phase 2 dose using non-weight-based dosing; (3) To characterize the PD profile of Antibody 1 on circulating levels of CSF-1; and (4) To assess the development of antibodies against Antibody 1 (immunogenicity).
  • Part A consists of dose escalation of Antibody 1 using weight-based dosing
  • Part B consists of dose escalation of Antibody 1 using non-weight-based dosing. Actual enrollment is dependent on the number of DLTs observed and the resultant size of each cohort.
  • Solid tumors include but are not limited to breast (including but not limited to triple negative, hormone receptor positive, HER2 over expressing, and hormone receptor expressing but without HER2 over expression), ovarian (including but not limited to fallopian tube cancer, primary peritoneal, and epithelia), melanoma, lung (including but not limited to non-small cell).
  • Dose cohorts, including revised dose and revised dosing schedule, are summarized in Table 1. For each cohort, one cycle is 6 weeks. In each cohort, subjects receive Antibody 1 by intravenous (IV.) infusion (with an observation period for weekly [QW] and every-2-week [Q2W] cohorts in Cycle 1 only, as described in Table 1).
  • IV. intravenous
  • CK creatine kinase
  • the dosing scheme and schedule for Study JSCA were revised to reflect dose reductions and prolonged administration intervals.
  • the dosages for subsequent dose explorations were as follows: Cohort 2 (0.3 mg/kg QW), Cohort 3 (0.6 mg/kg QW), Cohort 4 (1.25 mg/kg Q2W), Cohort 5 (1.25 mg/kg QW), and Cohort 6 (2.5 mg/kg Q2W) as shown in Table 1.
  • Consistent blockade of the CSF-1R signaling pathway is demonstrated by persistent elevation of circulating CSF-1 levels as well as reduction of the number of circulating non-classical/inflammatory monocytes, (CD14 dim CD 16 nght cells in peripheral circulation as determined by fluorescent antibody cell sorting (FACS)).
  • FACS fluorescent antibody cell sorting
  • increases in CSF-1 serum and decreases in CD14 dim CD16 nght cells in peripheral circulation are measures of the PD effect of Antibody 1.
  • the recommended phase 2 dose initially determined in Part A of Study JSCA was 1.25mg/kg Q2W.
  • subsequent PD and PK analyses of the preliminary data revealed intermittent target engagement with every 2 week dosing (dose level 4) compared to weekly dosing (dose level 5); as well as minimal correlation for drug clearance and body weight. Tables 2, 3, 6 and 7 provide preliminary patient specific results.
  • Table 6 FACS Results CD14 Dim CD16 Bnght ) at Dose Level 4 (1.25mg/kg Q2W)
  • Table 7 FACS Results CD14 Dim CD16 Bnght ) at Dose Level 5 (1.25mg/kg QW)
  • Table 8 FACS Results (CD14 Dim CD16 Bnght ) at Dose Level 6a (lOOmg QW)
  • a dose regimen of about 100 mg every week was determined to be safe and thus has become the recommended phase 2 dose.
  • the primary objectives are to document the immunomodulatory activity of Antibody 1 treatment in patients with advanced, refractory breast or prostate cancers, according to the following measures: (1) changes from baseline over time in peripheral blood immune cell subsets, as determined by flow cytometric analysis using an antibody panel; and (2) changes from baseline over time in serum cytokines, as determined by Meso Scale Discovery (MSD) multiplex cytokine immunoassay technology or ELISA.
  • MSD Meso Scale Discovery
  • the secondary objectives include but are not limited to are: (1) to evaluate the safety and toxicity profile of Antibody 1, as assessed by the Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0); (2) to assess the PK serum concentrations of Antibody 1; (3) to document antitumor activity, per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and immune-related RECIST (irRECIST); and (4) to assess the development of antibodies against Antibody 1 (immunogenicity), as assessed by a validated immunogenicity assay.
  • Antibody 1 in patients with advanced, refractory breast or prostate cancer. Eligible patients receive Antibody 1 as an infusion, suggested to be administered over approximately 90 minutes for the first infusion, decreasing by 30 minutes for subsequent infusions, until administered over 30 minutes.
  • Patients receive Dosage A, B, C, or D for one 6-week cycle or until the patient meets one or more criteria for study discontinuation. After 1 cycle, patients who are benefitting from study treatment (that is, no disease progression or unacceptable toxicity) may continue to receive study treatment at the same dose and schedule until there is clear (confirmed) evidence of disease progression or other withdrawal criteria are met. At the time of study completion, if a patient continues to benefit from study treatment, that patient may enter the continued access period.
  • the Antibody 1 dosing regimen of the present invention offers a safe and efficacious dose regime.
  • the present invention currently being explored in the Phase 1 Studies (JSCA, JSCB, JSCC), are expected to maximize the number of patients exposed to potentially therapeutic Antibody 1 serum levels, with minimal risk of increased toxicity, which can further optimize the benefit-risk ratio, and provide benefit for a patient population with a current unmet need.
  • the present invention provides an opportunity for improved patient outcomes, while minimizing risk of increased toxicity.
  • SEQ ID NO: 5 (HCDR1 Antibody 1)
  • SEQ ID NO: 6 (HCDR2 Antibody 1) VIWYDGSNKYYADSVKG
  • SEQ ID NO: 7 (HCDR3 Antibody 1)
  • SEQ ID NO: 8 (LCDR1 Antibody 1)

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Abstract

L'invention concerne un schéma posologique pour des anticorps humains qui se lient au récepteur du facteur-1 de stimulation anti-colonie humain (CSF-1R), de préférence l'anticorps 1.
PCT/US2018/015412 2017-02-02 2018-01-26 Schéma posologique pour anticorps anti-csf-1r WO2018144334A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3894014A4 (fr) * 2018-12-13 2022-04-20 Development Center for Biotechnology Anticorps anti-csf-1r humain et ses utilisations

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Publication number Priority date Publication date Assignee Title
WO2011123381A1 (fr) 2010-04-01 2011-10-06 Imclone Llc Anticorps contre le csf-1r
WO2013053767A1 (fr) * 2011-10-10 2013-04-18 Medimmune Limited Traitement de la polyarthrite rhumatoïde
WO2015036511A1 (fr) * 2013-09-12 2015-03-19 F. Hoffmann-La Roche Ag Thérapie combinatoire d'anticorps contre le csf-1 humain et d'anticorps contre le pd-l1r humain
WO2016168149A1 (fr) * 2015-04-13 2016-10-20 Five Prime Therapeutics, Inc. Polythérapie contre le cancer

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011123381A1 (fr) 2010-04-01 2011-10-06 Imclone Llc Anticorps contre le csf-1r
US8263079B2 (en) 2010-04-01 2012-09-11 ImClone, LLC Antibodies against CSF-1R
WO2013053767A1 (fr) * 2011-10-10 2013-04-18 Medimmune Limited Traitement de la polyarthrite rhumatoïde
WO2015036511A1 (fr) * 2013-09-12 2015-03-19 F. Hoffmann-La Roche Ag Thérapie combinatoire d'anticorps contre le csf-1 humain et d'anticorps contre le pd-l1r humain
WO2016168149A1 (fr) * 2015-04-13 2016-10-20 Five Prime Therapeutics, Inc. Polythérapie contre le cancer

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3894014A4 (fr) * 2018-12-13 2022-04-20 Development Center for Biotechnology Anticorps anti-csf-1r humain et ses utilisations
US12043668B2 (en) 2018-12-13 2024-07-23 Development Center For Biotechnology Anti-human CSF-1R antibody and uses thereof

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