WO2019114785A1 - Utilisation d'un anticorps anti-pd-1 dans le traitement d'une tumeur - Google Patents

Utilisation d'un anticorps anti-pd-1 dans le traitement d'une tumeur Download PDF

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WO2019114785A1
WO2019114785A1 PCT/CN2018/120819 CN2018120819W WO2019114785A1 WO 2019114785 A1 WO2019114785 A1 WO 2019114785A1 CN 2018120819 W CN2018120819 W CN 2018120819W WO 2019114785 A1 WO2019114785 A1 WO 2019114785A1
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antibody
antigen
binding fragment
ctla
seq
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PCT/CN2018/120819
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Chinese (zh)
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张力
方文峰
邹建军
杨清
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江苏恒瑞医药股份有限公司
中山大学附属肿瘤医院
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Priority to CN201880059067.9A priority Critical patent/CN111246881B/zh
Publication of WO2019114785A1 publication Critical patent/WO2019114785A1/fr

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    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • the present disclosure relates to the use of a PD-1 antibody for the preparation of a medicament for treating a tumor patient.
  • Cancer has many genetic and epigenetic changes that produce new antigens that can be recognized by the immune system.
  • the adaptive immune system including T and B lymphocytes, has potent anticancer potential, a wide range of capabilities and fine specificity in response to a variety of tumor antigens.
  • the immune system exhibits considerable plasticity and memory components. Successful use of all of these attributes of the adaptive immune system will make immunotherapy unique among all cancer treatment modalities.
  • Cancer immunotherapy has focused on methods for enhancing anti-tumor immune responses by adoptive transfer of activated effector cells, immunization against related antigens, or providing non-specific immunostimulatory agents such as cytokines.
  • specific immunological checkpoint pathway inhibitors has begun to become a new immunotherapy for cancer treatment, such as the CTLA antibody Ipilimumab for the treatment of advanced melanoma. (Hodi et al., 2010), specific binding to programmed death receptor (PD-1) nivolumab or pembrolizumab, and the like.
  • PD-1 antibody specifically recognizes and binds to PD-1 on the surface of lymphocytes, blocks the PD-1/PD-L1 signaling pathway, and activates the immune killing effect of T cells on tumors, and modulates the immune system of the body to eliminate tumor cells in vivo.
  • WO2015085847A discloses a novel anti-PD-1 antibody, which is in the clinical trial stage and has shown a certain anti-tumor effect.
  • Ipilimumab It is a humanized IgGl monoclonal antibody that blocks the binding of CTLA-4 to its B7 ligand, thereby stimulating T cell activation and improving overall survival (OS) in advanced melanoma patients (Hodi et al, 2010).
  • OS overall survival
  • Phase III clinical data showed that the overall survival of patients was significantly longer than that of Ipilimumab alone, in combination with Nivolumab for the treatment of melanoma (NCT01844505) (Wolchok et al., 2017).
  • such immunomodulatory therapeutic combinations have been carried out in combination, and no clinical reports have been reported in which an effective amount of PD-1 antibody is administered to a tumor patient who has not been relieved of treatment with a CTLA antibody.
  • the present disclosure provides the use of an anti-PD-1 antibody or antigen-binding fragment thereof for the preparation of a medicament for treating a tumor patient who has been treated with an anti-CTLA-4 antibody or antigen-binding fragment thereof.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is selected from the group consisting of AMP-224, GLS-010, IBI-308, REGN-2810, PDR-001, BGB-A317, Pidilizumab, PF-06801591, Genolimzumab, CA- 170, MEDI-0680, JS-001, TSR-042, Camrelizumab, Pembrolizumab, LZM-009, AK-103 and Nivolumab.
  • the light chain variable region of the anti-PD-1 antibody or antigen-binding fragment thereof comprises the LCDR1, LCDR2 as set forth in SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively And LCDR3;
  • the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as set forth in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively.
  • the PD-1 antibody is a humanized antibody.
  • the humanized antibody light chain variable region sequence is the sequence set forth in SEQ ID NO: 10 or a variant thereof, preferably having a 0-10 amino acid change in the light chain variable region, Preferably, the amino acid change of A43S; the humanized antibody heavy chain variable region sequence is the sequence set forth in SEQ ID NO: 9 or a variant thereof, preferably having 0-10 in the heavy chain variable region
  • the amino acid change is more preferably the amino acid change of G44R.
  • variable region sequences of the heavy and light chain of the humanized antibody of the PD-1 antibody of the present disclosure are as follows:
  • the humanized antibody light chain sequence is the sequence set forth in SEQ ID NO: 8 or a variant thereof; the variant preferably has a 0-10 amino acid change in the light chain variable region, more preferably Amino acid change of A43S; the humanized antibody heavy chain sequence is the sequence set forth in SEQ ID NO: 7 or a variant thereof, preferably having a 0-10 amino acid change in the heavy chain variable region, Amino acid changes of G44R are preferred.
  • the light chain sequence of the humanized antibody is the sequence set forth in SEQ ID NO: 8
  • the heavy chain sequence is the sequence set forth in SEQ ID NO: 7.
  • sequences of the humanized antibody heavy and light chains are as follows:
  • the anti-CTLA-4 antibody or antigen-binding fragment thereof competes with Ipilimumab for binding to human CTLA-4
  • the anti-CTLA-4 antibody or antigen-binding fragment thereof is chimeric, humanized or human Monoclonal antibodies or parts thereof.
  • the anti-CTLA-4 antibody or antigen-binding fragment thereof comprises a heavy chain constant region of a human IgGl isotype.
  • the anti-CTLA-4 antibody is selected from the group consisting of Ipilimumab, Tremelimumab, Belatacept or Abatacept.
  • the tumor is a malignant tumor or a benign tumor;
  • the malignant tumor is selected from the group consisting of a malignant epithelial tumor, a sarcoma, a myeloma, a leukemia, a lymphoma, a melanoma, a head and neck tumor, a brain tumor, a peritoneum Cancer, mixed tumor, childhood malignant tumor;
  • the malignant epithelial tumor is selected from the group consisting of lung cancer, breast cancer, liver cancer, pancreatic cancer, colorectal cancer, stomach cancer, gastroesophageal adenocarcinoma, esophageal cancer, small intestine cancer, cardiac cancer, endometrium Cancer, ovarian cancer, fallopian tube cancer, vulvar cancer, testicular cancer, prostate cancer, penile cancer, kidney cancer, bladder cancer, anal cancer, gallbladder cancer, cholangiocarcinoma, teratoma, cardiac tumor;
  • the head and neck tumor is selected from
  • the lung cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer
  • the breast cancer is selected from the group consisting of hormone receptor (HR) positive breast cancer, human epidermal growth factor receptor Body-2 (HER2)-positive breast cancer, triple-negative breast cancer
  • the renal cancer is selected from the group consisting of transparent renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting ductal carcinoma
  • said neuroepithelial neoplasm Selected from a preferred astrocytoma, anaplastic astrocytoma, glioblastoma
  • the liver cancer is selected from the group consisting of primary liver cancer, secondary liver cancer, and the primary liver cancer is selected from the group consisting of hepatocellular carcinoma and cholangiocarcinoma.
  • Cancer mixed liver cancer
  • the colorectal cancer is selected from the group consisting of colon cancer and rectal cancer.
  • the tumor is selected from the group consisting of Hodgkin's lymphoma, non-Hodgkin's lymphoma, prostate cancer, pancreatic cancer, lung cancer, esophageal cancer, liver cancer, cholangiocarcinoma, breast cancer, colorectal cancer , gastric cancer, kidney cancer, acute myeloid lymphocytic leukemia, myelodysplastic syndrome, glioma, nasopharyngeal carcinoma, tumor with unknown origin.
  • the anti-CTLA-4 antibody or antigen-binding fragment thereof of the present disclosure has a dose of 0.1 to 10.0 mg/kg, and may be 0.1 mg/kg, 0.2 mg/kg, 0.3 mg/kg, 0.4 mg/kg, 0.5 mg.
  • /kg 0.6mg/kg, 0.7mg/kg, 0.8mg/kg, 0.9mg/kg, 1.0mg/kg, 1.2mg/kg, 1.4mg/kg, 1.6mg/kg, 1.8mg/kg, 2.0mg /kg, 2.2mg/kg, 2.4mg/kg, 2.6mg/kg, 2.8mg/kg, 3.0mg/kg, 3.2mg/kg, 3.4mg/kg, 3.6mg/kg, 3.8mg/kg, 4.0mg /kg, 4.2mg/kg, 4.4mg/kg, 4.6mg/kg, 4.8mg/kg, 5.0mg/kg, 5.2mg/kg, 5.4mg/kg, 5.6mg/kg, 5.8mg/kg, 6.0mg /kg, 6.2mg/kg, 6.4mg/kg, 6.6mg/kg, 6.8mg/kg, 7.0mg/kg, 7.2mg
  • the anti-CTLA-4 antibody or antigen-binding fragment thereof is in the range of 1 to 600 mg, and may be 1.0 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg, 2.0 mg, 2.2 mg, 2.4mg, 2.6mg, 2.8mg, 3.0mg, 3.2mg, 3.4mg, 3.6mg, 3.8mg, 4.0mg, 4.2mg, 4.4mg, 4.6mg, 4.8mg, 5.0mg, 5.2mg, 5.4mg, 5.6mg 5.8mg, 6.0mg, 6.2mg, 6.4mg, 6.6mg, 6.8mg, 7.0mg, 7.2mg, 7.4mg, 7.6mg, 7.8mg, 8.0mg, 8.2mg, 8.4mg, 8.6mg, 8.8mg, 9.0 Mg, 9.2 mg, 9.4 mg, 9.6 mg, 9.8 mg, 10.0 mg, 15 mg, 20
  • the anti-PD-1 antibody or antigen-binding fragment thereof has a dose of 0.1 to 10.0 mg/kg, and may be 0.1 mg/kg, 0.2 mg/kg, 0.3 mg/kg, 0.4 mg/ Kg, 0.5mg/kg, 0.6mg/kg, 0.7mg/kg, 0.8mg/kg, 0.9mg/kg, 1.0mg/kg, 1.2mg/kg, 1.4mg/kg, 1.6mg/kg, 1.8mg/ Kg, 2.0 mg/kg, 2.2 mg/kg, 2.4 mg/kg, 2.6 mg/kg, 2.8 mg/kg, 3.0 mg/kg, 3.2 mg/kg, 3.4 mg/kg, 3.6 mg/kg, 3.8 mg/ Kg, 4.0 mg/kg, 4.2 mg/kg, 4.4 mg/kg, 4.6 mg/kg, 4.8 mg/kg, 5.0 mg/kg, 5.2 mg/kg, 5.4 mg/kg, 5.6 mg/kg, 5.8 mg/ Kg
  • the PD-1 antibody or antigen-binding fragment thereof has a dose of 1 to 600 mg, and may be 1.0 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg, 2.0 mg, 2.2, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.6, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8 5.6mg, 5.8mg, 6.0mg, 6.2mg, 6.4mg, 6.6mg, 6.8mg, 7.0mg, 7.2mg, 7.4mg, 7.6mg, 7.8mg, 8.0mg, 8.2mg, 8.4mg, 8.6mg, 8.8 Mg, 9.0 mg, 9.2 mg, 9.4 mg, 9.6 mg, 9.8 mg, 10.0 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg,
  • the anti-PD-1 antibody or antigen-binding fragment thereof of the present disclosure is administered once a week, once every two weeks, once every three weeks, once every four weeks, or once a month, and the anti-CTLA-4 antibody or antigen-binding fragment thereof
  • the frequency of administration is once a day, twice a day, three times a day, once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered in an amount of from 1 to 600 mg, and the anti-CTLA-4 antibody or antigen-binding fragment thereof is in a dose of from 3 to 10 mg/kg.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered in an amount of from 1 to 600 mg once every 1-4 weeks; and the anti-CTLA-4 antibody or antigen-binding fragment thereof is administered in an amount of from 3 to 10 mg/kg. Every once every 1-4 weeks.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is dosed 200 mg; the anti-CTLA-4 antibody or antigen-binding fragment thereof is administered at a dose of 3 to 10 mg/kg.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered in a dose of 200 mg once every 3 weeks; the anti-CTLA-4 antibody or antigen-binding fragment thereof is administered at a dose of 3 to 10 mg/kg every 3 weeks. once.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is dosed 200 mg once every 2 weeks; the anti-CTLA-4 antibody or antigen-binding fragment thereof is administered at a dose of 3 to 10 mg/kg every 3 weeks once.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 1 to 10.0 mg/kg once every 1-4 weeks; and the anti-CTLA-4 antibody or antigen-binding fragment thereof has a dose of 1 ⁇ 10.0mg/kg, once every 1-4 weeks.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10.0 mg/kg once every 2 weeks; and the anti-CTLA-4 antibody or antigen-binding fragment thereof is administered at a dose of 3 to 10 mg/kg. Every once every 1-4 weeks.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is at a dose of 1 mg/kg and the anti-CTLA-4 antibody or antigen-binding fragment thereof is at a dose of 3 mg/kg.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 1 mg/kg once every 3 weeks; the anti-CTLA-4 antibody or antigen-binding fragment thereof is administered at a dose of 3 mg/kg per 3 Once a week.
  • the administration route of the present disclosure may be oral administration, parenteral administration, or transdermal administration, and the parenteral administration includes, but not limited to, intravenous injection, subcutaneous injection, and intramuscular injection.
  • the PD-1 antibody or CTLA-4 antibody is administered by injection, for example subcutaneously or intravenously, and the PD-1 antibody or CTLA-4 antibody is formulated into an injectable form prior to injection.
  • a particularly preferred injectable form of the PD-1 antibody or CTLA-4 antibody is an injectable or lyophilized powder, such as an injectable form of a PD-1 antibody, comprising a PD-1 antibody, a buffer, a stabilizer, optionally The ground also contains a surfactant.
  • the buffering agent may be selected from one or more of the group consisting of acetate, citrate, succinate, and phosphate.
  • the stabilizer may be selected from sugars or amino acids, preferably disaccharides such as sucrose, lactose, trehalose, maltose.
  • the surfactant is selected from the group consisting of polyoxyethylene hydrogenated castor oil, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, preferably the polyoxyethylene sorbitan fatty acid ester is polysorbate 20, 40, 60 or 80. Most preferred is polysorbate 20.
  • the tumor patients described in the present disclosure have also been treated with other anticancer agents, including receiving other anticancer agents prior to treatment with anti-CTLA-4 antibodies or antigen-binding fragments thereof, or receiving anti-CTLA-4 antibodies or antigen-binding fragments thereof. Treated with other anticancer agents after treatment.
  • anticancer agents described in the present disclosure are compounds useful for treating cancer, selected from, but not limited to, alkylating agents such as thiotepa, cyclophosphamide, ifosfamide; alkyl sulfonates such as busulfan , Ying Bing Shu Fan and Pipershufan; aziridines, such as benzodiazepam, carbazone, meturedopa and uredopa; methyl melamines, including altretamine, triethylenemelamine, trietylenephosphoramide, tri-ethyl thiophosphoramide (triethiylenethiophosphoramide) and trimethylolomelamine; beta-lapachone; lapachol; colchicine; betulinic acid; camptothecin (camptothecin) Including synthetic analogues topotecan, CPT-11 (irinotecan, acetylcamptothecin, scopolectin and 9-aminocamptothec
  • the target lesion diameter of the tumor patient of the present disclosure is relatively reduced by at least 30%.
  • the tumor patient of the present disclosure has a relative increase in target lesion diameter of at least 20% or the appearance of one or more new lesions.
  • the target lesion diameter of the tumor patient of the present disclosure is relatively increased by up to 20% or the target lesion diameter is relatively reduced by up to 30%.
  • tumor patient of the present disclosure is therapeutically unsuccessful.
  • the disclosure also provides a method of treating a tumor, the method comprising:
  • the swollen patient has also been treated with other anticancer agents.
  • the tumor patient has a relative increase in target lesion diameter of at least 20% or the presence of one or more new lesions.
  • the tumor patient has a relative reduction in target lesion diameter of at least 30%.
  • the tumor patient has a relative increase in target lesion diameter of at most 20% or a targeted lesion diameter that is relatively reduced by up to 30%.
  • the tumor patient is treatment failure.
  • the "humanized antibody”, also referred to as a CDR-grafted antibody, refers to the transplantation of a mouse CDR sequence into a human antibody variable region framework, ie, a different type.
  • An antibody produced in a human germline antibody framework sequence It is possible to overcome the strong antibody variable antibody response induced by chimeric antibodies by carrying a large amount of mouse protein components.
  • Such framework sequences can be obtained from public DNA databases including germline antibody gene sequences or published references.
  • the germline DNA sequences of human heavy and light chain variable region genes can be found in the "VBase" human germline sequence database (available on the Internet at www.mrccpe.com.ac.uk/vbase), as well as in Kabat, EA, etc.
  • the CDR sequence of the PD-1 humanized antibody is selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6.
  • an "antigen-binding fragment” as used in the present disclosure refers to a Fab fragment having antigen-binding activity, a Fab' fragment, an F(ab')2 fragment, and an Fv fragment sFv fragment that binds to human PD-1; comprising the antibody of the present disclosure One or more CDR regions selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 6.
  • the Fv fragment contains the antibody heavy chain variable region and the light chain variable region, but has no constant region and has the smallest antibody fragment of the entire antigen binding site.
  • Fv antibodies also comprise a polypeptide linker between the VH and VL domains and are capable of forming the desired structure for antigen binding.
  • the two antibody variable regions can also be joined by a different linker into a single polypeptide chain, referred to as a single chain antibody or a single chain Fv (sFv).
  • binding to PD-1 refers to the ability to interact with human PD-1.
  • antigen binding site refers to a three-dimensional spatial site that is discrete on an antigen and that is recognized by an antibody or antigen-binding fragment of the present disclosure.
  • Immunotherapy as used in the present disclosure means that immunotherapy is the use of the immune system to treat diseases. In the present disclosure, it mainly refers to stimulating and enhancing the body's anti-tumor immune response by increasing the immunogenicity of tumor cells and sensitivity to effector cell killing. And use immune cells and effector molecules to infuse the host, and cooperate with the body's immune system to kill tumors and inhibit tumor growth.
  • an "effective amount” as used in the present disclosure includes an amount sufficient to ameliorate or prevent a symptom or condition of a medical condition.
  • An effective amount also means an amount sufficient to allow or facilitate the diagnosis.
  • An effective amount for a particular patient or veterinary subject can vary depending on factors such as the condition to be treated, the overall health of the patient, the route and dosage of the method of administration, and the severity of the side effects.
  • An effective amount can be the maximum dose or dosing regimen that avoids significant side effects or toxic effects.
  • Treatment failure means that the subject is accompanied by a measurable tumor lesion at baseline and is disease progression (PD) or intolerable according to the RECIST 1.1 efficacy assessment criteria.
  • Untolerable as used in the present disclosure means that the adverse reactions caused by the drug cannot continue to be treated.
  • Total survival refers to the period from random period to death from any cause. For subjects who survived at the last follow-up, their OS was censored as data at the last follow-up. In the subjects who were lost to follow-up, the OS was counted as data censored by the last confirmed survival time before the loss of follow-up.
  • the data censored OS is defined as the time from random grouping to censoring.
  • Objective response rate refers to the proportion of patients whose tumor shrinks to a certain extent and remains for a certain period of time, including cases of CR and PR.
  • Tumor remission assessment criteria (RECIST 1.1 criteria) were used to assess objective tumor remission. Subjects must be accompanied by measurable tumor lesions at baseline, and the efficacy criteria were divided into complete response (CR), partial response (PR), stable (SD), and progression (PD) according to RECIST 1.1 criteria.
  • DCR Disease Control Rate
  • CR Complete remission
  • Partial remission The sum of the target lesion diameters is at least 30% less than the baseline level.
  • PD Disease progression: reference to the minimum of the sum of all measured target lesion diameters throughout the experimental study, with a diameter and relative increase of at least 20% (referenced to baseline values if the baseline measurement is minimal); In addition, the absolute value of the diameter and the absolute value must be increased by at least 5 mm (one or more new lesions are also considered to be disease progression).
  • Stable disease The extent of target lesion reduction did not reach PR, and the degree of increase did not reach PD level. Between the two, the minimum value of the sum of diameters could be used as a reference.
  • anticancer agents used in the present disclosure are commercially available.
  • Figure 1 Comparison of volume of abdominal wall metastases before and after PD-1 treatment.
  • Compound A (Ipilimumab): a dose of 3 mg / kg or 10 mg / kg;
  • Compound B (PD-1, prepared according to the method of patent application WO2017054646A): a dose of 200 mg or 10 mg/kg;
  • Patient 1 After 6 courses of treatment with Compound A, the disease progresses, the disease is stable after 3 courses of intervening chemotherapy (cisplatin), and then compound B (intravenous infusion, once every 2 weeks, 4 weeks for one cycle) After 2 cycles, the sum of the diameters of the target lesions (left 8 rib soft tissue, spleen 1, spleen 2) was at least 32% lower than the baseline level, and the disease was partially relieved;
  • Patient 2 After 4 courses of treatment with Compound A, the disease was stable, and the disease progressed after withdrawal from the test, and Compound B (intravenous infusion, once every 2 weeks, 4 weeks for one cycle) was given for 6 cycles.
  • the sum of the diameters of the target lesions (liver, rhomboid nodules, subganglia muscle nodules) was 32% lower than the baseline level, and the disease was partially relieved;
  • Patient 3 After 4 courses of treatment with Compound A, the disease progresses, and then compound B (intravenous infusion, once every 2 weeks, 4 weeks for one cycle) after 2 cycles of treatment, the patient's target lesion (negative liver and abdominal aorta) The sum of the diameters of the lymph nodes was 38% lower than the baseline level, and the disease was partially relieved;
  • Patient 5 After 4 courses of treatment with Compound A, disease progression, intervening chemotherapy (capecitabine) for 8 courses, then compound B (intravenous infusion, once every 2 weeks, 4 weeks for one cycle) After 2 cycles, the sum of the diameters of the target lesions (liver S3, liver S5, peritoneal mass) was 62% lower than the baseline level, and the disease was partially relieved, see Figure 1;
  • Patient 6 After 4 courses of treatment with Compound A, disease progression, intervening chemotherapy (gemcitabine + vincristine), after 6 courses of treatment, the disease was stable, and then used Teggio, then compound B (intravenous infusion, each 2 weeks, 4 weeks for a cycle) After 2 cycles of treatment, the patient's target lesion (middle left middle lobe, right middle lobe) diameter increased by 20% than the baseline level, disease progression;
  • Patient 7 After 4 courses of treatment with Compound A, disease progression, intervening chemotherapy (Tiggio) 5 courses, disease progression, and then compound B (intravenous drip, once every 2 weeks, 4 weeks for a cycle) After treatment, the sum of the target lesions (left lung, liver S4 segment, liver S2 segment, right adrenal gland) increased by 22% compared with baseline levels, disease progression;
  • Patient 8 After treatment with Compound A (February), disease progression, and then compound B (intravenous infusion, once every 2 weeks, 4 weeks for one cycle) after 2 cycles of treatment, the target lesion (right lung) diameter It is 43% lower than the limit level and the disease is partially relieved.

Abstract

L'invention concerne une utilisation d'un anticorps anti-PD-1 dans le traitement d'une tumeur. En particulier, l'invention concerne une utilisation d'un anticorps anti-PD-1, ou d'un fragment de liaison à l'antigène associé, dans la préparation d'un médicament pour le traitement d'un patient atteint d'une tumeur ayant reçu un traitement avec un anticorps anti-CTLA-4 ou un fragment de liaison à l'antigène associé.
PCT/CN2018/120819 2017-12-14 2018-12-13 Utilisation d'un anticorps anti-pd-1 dans le traitement d'une tumeur WO2019114785A1 (fr)

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CN114470216A (zh) * 2020-10-23 2022-05-13 和记黄埔医药（上海）有限公司 多受体酪氨酸激酶抑制剂与化疗剂的药物组合及其使用方法

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