WO2024027599A1 - Biomarqueur pour prédire la sensibilité du cancer du rectum au traitement par an0025 en combinaison avec la radiothérapie/chimioradiothérapie (rt/crt) - Google Patents

Biomarqueur pour prédire la sensibilité du cancer du rectum au traitement par an0025 en combinaison avec la radiothérapie/chimioradiothérapie (rt/crt) Download PDF

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WO2024027599A1
WO2024027599A1 PCT/CN2023/109888 CN2023109888W WO2024027599A1 WO 2024027599 A1 WO2024027599 A1 WO 2024027599A1 CN 2023109888 W CN2023109888 W CN 2023109888W WO 2024027599 A1 WO2024027599 A1 WO 2024027599A1
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patient
radiotherapy
chemoradiotherapy
crt
rectal cancer
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PCT/CN2023/109888
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English (en)
Chinese (zh)
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梁洪铭
卢煦阳
劳特米尔克内森
爱金逊罗伯特
汤凯扬
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杭州阿诺生物医药科技有限公司
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Priority to CN202380010282.0A priority Critical patent/CN117242348A/zh
Publication of WO2024027599A1 publication Critical patent/WO2024027599A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the invention relates to the biological field and involves a series of biomarkers that can be used to predict the sensitivity of rectal cancer patients to AN0025 combined radiotherapy/chemoradiotherapy (RT/CRT) treatment.
  • RT/CRT radiotherapy/chemoradiotherapy
  • Rectal cancer is one of the common malignant tumors in middle-aged and elderly people, and it most commonly occurs over the age of 50. With the changes in people's eating habits and structure and the aging of the population, its incidence rate is on the rise.
  • the main treatment methods for rectal cancer also include targeted therapy, gene therapy, traditional Chinese medicine treatment, immunotherapy, etc. At present, surgery is still the first choice treatment and the only means to cure rectal cancer.
  • surgery is still the first choice treatment and the only means to cure rectal cancer.
  • some patients cannot undergo surgical treatment, and some patients cannot undergo repeated surgical treatment.
  • radiotherapy or chemoradiotherapy is the main treatment method, with the purpose of improving the patient's survival rate and quality of life.
  • AN0025 is a highly selective and highly active antagonist of prostaglandin E2 (PGE2) receptor 4 (EP4) developed by Arnold Pharmaceuticals. It can inhibit the signaling pathway mediated by PGE2-EP4.
  • Myeloid cells are the most important immune cells infiltrating tumors, mainly including tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC). TAM and MDSC are differentiated from immature monocytes.
  • EP4 is one of the four PGE2 receptors. It is expressed on myeloid cells and plays a key role in promoting the differentiation of monocytes into TAMs and MDSCs in the tumor microenvironment.
  • the signaling pathway composed of prostaglandin E2 (PGE2) and its subtype 4 receptor (EP4) can not only promote the occurrence of cancer, but also form a cancer microenvironment that promotes cancer development and suppresses immunity.
  • cAMP produced by the activation of the PGE2/EP4 signaling pathway in T cells can activate the cAMP-PKA signaling pathway, and this process can effectively inhibit the function of T cells.
  • the PGE2/EP4 signaling pathway can also negatively regulate the maturation of DCs and induce the formation of a variety of immunosuppressive cells including M2 macrophages and myeloid suppressor cells (MDSC) ( S et al. Front Immunol. 2019;10:475).
  • MDSC myeloid suppressor cells
  • the compound (AN0025) with the structure of formula (I) and its pharmaceutically acceptable salts is a highly selective small molecule inhibitor targeting E-type prostaglandin receptor 4.
  • AN0025 can effectively reduce immunosuppressive cells in the tumor microenvironment by inhibiting the PGE2/EP4 signaling pathway.
  • AN0025 has been used in multiple clinical strategies.
  • FIH first in human
  • AN0025 has demonstrated certain single-agent efficacy
  • AN0025 has shown great efficacy in combination with radiotherapy and chemotherapy. Strong clinical efficacy (Wyrwicz et.al, Poster#540, ESMO2019).
  • the present invention provides a series of biomarker applications, aiming to solve the problem of predicting the sensitivity of rectal cancer patients to AN0025 combined radiotherapy/chemoradiotherapy (RT/CRT), so as to screen out more suitable treatment options. group of patients with rectal cancer to further improve the targeting of therapy.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the invention provides a method of detecting IL-1 alpha, IL-4, IL-18, IL-27a, EGF, HGF, VEGF-D, SCF, IFN-gamma, MCP-1 in blood samples of patients with rectal cancer.
  • the invention provides IL-1 alpha, IL-4, IL-18, IL-27a, EGF, HGF, VEGF-D, SCF, IFN-gamma, MCP-1 (CCL2 ) or CCL11
  • (Eotaxin) as a biomarker in the preparation of products for predicting the patient's sensitivity to AN0025 combined radiotherapy/chemoradiotherapy (RT/CRT).
  • the above application provided by the present invention includes the following steps:
  • Step 1 Centrifuge the peripheral blood samples to be tested from patients with rectal cancer to collect plasma
  • Step 2 Detect IL-1 alpha, IL-4, IL-18, IL-27a, EGF, HGF, VEGF-D, SCF, IFN-gamma, MCP-1 (CCL2) or CCL11 (Eotaxin) in the plasma concentration;
  • Step 3 If the plasma detection concentration is higher than the reference value, the rectal cancer patient is considered to be sensitive to AN0025 combined radiotherapy/chemoradiotherapy (RT/CRT) treatment; otherwise, the patient is insensitive.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention provides the use of CD8, CD3&CD8, CD3&CD8&PD-1 in tumor tissue samples of rectal cancer patients as biomarkers for predicting the sensitivity of the patient to AN0025 combined radiotherapy/chemoradiotherapy (RT/CRT) treatment.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention provides CD8, CD3&CD8, CD3&CD8&PD-1 in tumor tissue samples of rectal cancer patients as biomarkers for preparing the patient's sensitivity to AN0025 combined radiotherapy/chemoradiotherapy (RT/CRT). application in the product.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the above-mentioned application provided by the present invention includes the following steps:
  • Step 1 Process the tumor tissue samples from rectal cancer patients according to the ELISE method
  • Step 2 Detect the expression levels of CD3, CD8, and PD-1 in the tissue sample
  • Step 3 If the detected expression levels of CD8, CD3&CD8, CD3&CD8&PD-1 are higher than the reference value, the rectal cancer patient is considered to be sensitive to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT); otherwise, the patient is insensitive.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention provides a method for predicting the sensitivity of colorectal patients to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT), including selecting the above-mentioned blood biomarkers IL-1 alpha, IL-4 of the patient , one or more of IL-18, IL-27a, EGF, HGF, VEGF-D, SCF, IFN-gamma, MCP-1 (CCL2) or CCL11 (Eotaxin), and/or such as the patient's tumor tissue One or more of the biomarkers CD8, CD3&CD8, CD3&CD8&PD-1.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention also provides a method for treating patients with rectal cancer, comprising the following steps:
  • Step 1 According to the method of claim 7, predict the sensitivity of colorectal patients to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT);
  • Step 2 If the rectal cancer patient is predicted to be treated with AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT) If the sensitivity is high, a therapeutically effective dose of AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT) will be administered to the patient with rectal cancer.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention provides a method of treating a rectal cancer patient in need thereof, comprising: administering to the rectal cancer patient a therapeutically effective amount of AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT), wherein the The patient was predicted to be sensitive to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT) by the aforementioned method.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention provides a method of treating a rectal cancer patient in need thereof, comprising: administering a therapeutically effective amount of AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT) to the rectal cancer patient, wherein, Detection concentrations of IL-1 alpha, IL-4, IL-18, IL-27a, EGF, HGF, VEGF-D, SCF, IFN-gamma, MCP-1 (CCL2) or CCL11 (Eotaxin) in the patient's blood samples is higher than its reference value, and/or the expression of CD8, CD3&CD8, CD3&CD8&PD-1 in the patient's tumor tissue sample is higher than its reference value.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the "reference value” refers to the specific value with which the detection value is compared to determine whether the patient is responsive or sensitive to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT) treatment, which can be obtained, for example, through clinical statistical analysis.
  • RT/CRT radiotherapy/chemoradiotherapy
  • the present invention also provides a kit for predicting the sensitivity of rectal cancer patients to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT), which kit includes the patient's blood biomarker as described above. one or more, and/or one or more biomarkers of the patient's tumor tissue as described above.
  • R/CRT radiotherapy/chemoradiotherapy
  • Figure 1 shows the content of each biomarker in the blood samples of patients with complete pathological response (pCR)/complete clinical response (cCR) and no complete response (non-CR), with the Y-axis unit pg/mL.
  • Figure 2 shows the proportion of positive cells for each biomarker in total cells in tumor tissue samples from patients with complete pathological response (pCR)/complete clinical response (cCR) and no complete response (non-CR).
  • the Y-axis represents the percentage. .
  • biomarker is equivalent to a biomarker or a molecular marker, which is any gene or protein whose expression level in a tissue or cell is altered compared to the expression level of a normal or healthy cell or tissue, ( used alone or in combination with other qualitative terms such as breast cancer marker, breast cancer-specific marker, control marker, exogenous marker, endogenous marker) refers to something that is measurable, calculable, or otherwise obtainable, and is associated with any Parameters related to molecules or combinations of molecules that can be used as indicators of biological and/or chemical states.
  • marker refers to a parameter associated with one or more biological molecules (i.e., “biomarker”) such as natural or synthetically produced nucleic acids (i.e., individual genes, as well as coding and non-coding DNA and RNA) and proteins (e.g., peptides, polypeptides).
  • biomarker in the present invention also includes reference to a single parameter that can be calculated or otherwise obtained by considering expression data from two or more different markers.
  • IL-1 alpha/IL-4/IL-18/IL-27a/EGF/HGF/VEGF-D/SCF/IFN-gamma/MCP-1(CCL2)/CCL11(Eotaxin) of the present invention is a blood sample biomarker substances, including IL-1 alpha/IL-4/IL-18/IL-27a/EGF/HGF/VEGF-D/SCF/IFN-gamma/MCP-1(CCL2)/CCL11( Eotaxin) protein sequence, also encompasses the amino acid sequence of its variants and/or homologs, and proteins with at least 80%, at least 85%, at least 90% or at least 95% homology to fragments of that sequence, provided that the variant Body proteins (including isotypes), homologous proteins and/or fragments are affected by one or more IL-1 alpha/IL-4/IL-18/IL-27a/EGF/HGF/VEGF-D/SCF/IFN -gamma/MCP-1(CCL2)/CCL
  • CD3/CD8/PD-1 of the present invention is a tissue sample biomarker, covering, for example, the CD3/CD8/PD-1 protein sequence included in databases such as Uniprot, and also covering the amino acid sequences of its variants and/or homologues, and proteins with fragments of that sequence having at least 80%, at least 85%, at least 90% or at least 95% homology, provided that variant proteins (including isotypes), homologous proteins and/or fragments are affected by one or Recognized by multiple CD3/CD8/PD-1 specific antibodies.
  • an amino acid or nucleic acid sequence has a certain degree of identity with an amino acid or nucleic acid sequence as described herein
  • the skilled person can use means and methods well known in the art, such as alignment, either manually or by using Computer programs known in the art or described herein.
  • the term "identical” or “percent identity” in the context of two or more amino acid or nucleic acid sequences means as measured using sequence comparison algorithms known in the art or by manual alignment and visual inspection.
  • two or more sequences or subsequences that are identical, or a specified percentage of amino acid residues or nucleotides are identical are considered to have, for example, 60% when compared and aligned over a comparison window or over a specified region for maximum correspondence to 95% or more Sequences with large sequence identity are essentially identical.
  • sequences with large sequence identity are essentially identical.
  • sequences with large sequence identity are essentially identical.
  • sequences with large sequence identity are essentially identical.
  • the described identity exists over a region of at least about 15 to 25 amino acids or nucleotides in length, more preferably about 50 to 100 amino acids or nucleotides in length.
  • Rectal cancer in the present invention refers to malignant tumors of the digestive tract occurring in the colon or rectum. Rectal cancer occurs when the cells lining the colon behave abnormally or grow into polyps. If polyps are not treated, they can turn into cancer. It includes but is not limited to various pathological types such as adenocarcinoma and squamous cell carcinoma.
  • Radiotherapy refers to the medical use of ionizing radiation, especially for the treatment of cancer.
  • the medical use of ionizing radiation in cancer treatment results in the reduction and/or killing of cancer cells in a subject.
  • Radiation therapy can be administered by any means known to those skilled in the art. Examples of radiation utilized in radiotherapy include, but are not limited to, photon radiation, ionizing radiation, or charged particle radiation, such as X-rays or protons. Examples of radiation therapy include, but are not limited to: external beam radiation therapy or teletherapy; brachytherapy or sealed beam source therapy; and whole body radioactive isotope therapy or unsealed source radiation therapy.
  • “Chemotherapy” in the present invention also known as “chemotherapy” refers to the use of chemotherapeutic agents to treat cancer subjects, wherein the chemotherapeutic agents include those commonly used for cancer patients so far, such as taxanes, paclitaxel, Docetaxel, cabazitaxel, gemcitabine, carboplatin, cisplatin, oxaliplatin, fluorouracil, capecitabine, or tegafur, or any functional analog thereof.
  • the chemotherapeutic agent of the invention is selected from capecitabine or leucovorin/5-fluoropyrimidine/oxaliplatin (mFOLFOX-6).
  • Radiotherapy in the present invention refers to administering radiotherapy and chemotherapy to treat cancer patients at the same time or at different time points.
  • Treatment refers to reducing, inhibiting, and/or reversing the progression of a disease (eg, tumor/cancer) in a subject in need thereof.
  • treatment includes any indication of successful treatment or improvement of a disease, including any objective or subjective parameter, such as alleviation; alleviation; reduction of symptoms or making the injury, pathology or disorder more tolerable to the subject; delaying or slowing the rate of progression, etc. Measurement of treatment or improvement may be based, for example, on the results of physical, pathological, and/or diagnostic examinations known in the art.
  • Treatment may also refer to reducing the onset or risk of a disease, or reducing the recurrence of the disease (eg, prolonging the time to recurrence) compared to what would occur if the measure was not taken. In the medical field, this treatment is also called “prophylaxis.”
  • subject refers to a mammalian subject, and in particular a human subject, including male or female subjects, and includes newborn, infant, toddler, adolescent, adult or geriatric subjects, and further includes various human races and ethnicities, e.g. Caucasian, African and Asian races.
  • salts refers to relatively non-toxic inorganic or organic acid salts of the compounds of formula I of the present invention. This These salts may be prepared in situ during the final isolation and purification of the compound, or by reacting the free form of the purified compound with a suitable organic or inorganic acid, respectively, and isolating the salt so formed.
  • Representative acid salts include, but are not limited to, acetate, adipate, aspartate, benzoate, benzenesulfonate, bicarbonate/carbonate, bisulfate/sulfate , borate, dextrorotary camphorsulfonate, citrate, cyclosulfonate, ethanedisulfonate, ethanesulfonate, formate, fumarate, glucoheptonate, gluconic acid Salt, glucuronate, hexafluorophosphate, hypobenrate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactic acid Salt, malate, maleate, malonate, methanesulfonate, methylsulfate, naphthylate, 2-naphthalenesulfonate, nicotinate, nitrate, orotic acid Salt, oxalate
  • pharmaceutically acceptable and “pharmaceutically acceptable” are used interchangeably and refer to those generally accepted by those skilled in the pharmaceutical art.
  • pharmaceutically acceptable salts pharmaceutically acceptable carriers, etc.
  • an “effective amount” or “therapeutically effective amount” refers to an amount effective in treating a disease as documented through clinical testing and evaluation, patient observation, and the like. “Effective amount” may further mean an amount that causes a detectable change in biological or chemical activity. Detectable changes can be detected and/or further quantified by one skilled in the art familiar with the relevant mechanisms or methods. Additionally, an “effective amount” may mean an amount that maintains a desired physiological state (i.e., reduces or prevents significant decline and/or promotes improvement of a condition). "Effective amount” may further refer to a therapeutically effective amount.
  • WO2012039972 specifically describes the compound of formula I of the present invention.
  • the compound or its pharmaceutically acceptable salt and its preparation process are disclosed in the Examples of WO2012/039972, which is incorporated herein by reference in its entirety.
  • Negative controls should be species- and isotype-matched nonspecific immunoglobulins diluted in PBS-T.
  • the washing step is the same as step 4 of antigen coating.
  • the washing step is the same as step 4 of antigen coating.
  • biomarkers were detected, including: BDNF, EGF, CCL11 (Eotaxin), FGF-2, GM-CSF, GRO alpha (CXCL1), HGF, IFN alpha, IFN gamma, IL-1 alpha, IL-1 beta, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8(CXCL8), IL -9, IL-10, IL-12p70, IL-13, IL-15, IL-17A (CTLA-8), IL-18, IL-21, IL-22, IL-23, IL-27a, IL- 31, IP-10 (CXCL10), LIF, MCP-1 (CCL2), MIP-1 alpha (CCL3), MIP-1 beta (CCL4), NGF beta, PDGF-
  • Tissue samples were obtained from a multi-center clinical trial conducted in the United States, with the trial registration number ClinicalTrials.gov ID: NCT03152370.
  • Pretreatment Screening or baseline. Available archived tumor material may be submitted as a pretreatment biopsy, provided that local pathology review as defined in the laboratory manual meets minimum requirements. If archived tumor material is unavailable or does not meet minimum requirements, a new tumor biopsy must be performed according to local institutional practice; 2) before radiotherapy (week 2 [days 10-14]); 3) at the end of treatment (optional day 10-14) 10 weeks [+/-2]); 4) During surgery (weeks 14-16).
  • Negative controls should be species- and isotype-matched nonspecific immunoglobulins diluted in PBS-T.
  • the washing step is the same as step 4 of antigen coating.
  • the washing step is the same as step 4 of antigen coating.
  • Statistical analysis is used to compare whether there are differences in the expression of specific biomarkers between the patient group that achieves the best response and the patient group that has no response. A total of 6 different combinations of different types of biomarkers were tested, including: CD163, CD3, CD4, CD8, PD-1, and PD-L1.
  • test results are shown in Figure 2: The combination of these three biomarkers in the tumor tissues of patients with complete pathological response (pCR) or complete clinical response (cCR) was statistically significantly higher than that of patients with no complete response (non-CR). patient group. Among them, patients who test positive for CD8, patients who test positive for a combination of CD3 and CD8, and patients who test positive for CD3, CD8, and PD-1 can achieve better results during treatment. This also suggests that the three combinations of CD8, CD3&CD8, and CD3&CD8&PD-1 can be used to predict the efficacy of patient populations.
  • one or more of the blood biomarkers as shown in Figure 1 and one or more of the tumor tissue biomarkers as shown in Figure 2 of patients with rectal cancer can be selected in combination to further improve The accuracy of predicting the sensitivity of this rectal cancer patient to AN0025 combined with radiotherapy/chemoradiotherapy (RT/CRT).
  • RT/CRT radiotherapy/chemoradiotherapy

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Abstract

La présente invention concerne l'utilisation de l'IL-1 alpha, de l'IL-4, de l'IL-18, de l'IL-27a, de l'EGF, de l'HGF, du VEGF-D, du SCF, de l'IFN-gamma et du MCP-1 (CCL2) ou du CCL11 (Eotaxine) dans des échantillons sanguins et du CD8, du CD3&CD8 et du CD3&CD8&PD-1 dans des échantillons de tissus tumoraux d'un patient atteint d'un cancer du rectum comme biomarqueur pour prédire la sensibilité du patient au traitement par AN0025 en association avec une radiothérapie/chimioradiothérapie (RT/CRT), et ses étapes, ainsi qu'un procédé pour prédire la sensibilité d'un patient atteint d'un cancer du rectum au traitement par AN0025 en association avec une radiothérapie/chimioradiothérapie (RT/CRT) et une méthode de traitement d'un patient atteint d'un cancer du rectum selon son utilisation.
PCT/CN2023/109888 2022-08-04 2023-07-28 Biomarqueur pour prédire la sensibilité du cancer du rectum au traitement par an0025 en combinaison avec la radiothérapie/chimioradiothérapie (rt/crt) WO2024027599A1 (fr)

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