Pharmaceutical combinations for treatment of uterine malignancies

Abstract

Provided is a pharmaceutical composition for the treatment of uterine malignant tumors, comprising an anti-PD-L1 antibody or an antigen binding fragment thereof and a chemotherapeutic drug, optionally comprising anlotinib or a pharmaceutically acceptable salt thereof; and the use of the pharmaceutical composition for the treatment of uterine malignant tumors.

Description

Drug combinations for treating uterine malignancies

[0001] This disclosure claims priority to a Chinese patent application filed with the China Patent Office on June 2, 2022, with application number 202210629630.X and invention name “Drug Combination for Treating Endometrial Cancer,” the entire contents of which are incorporated by reference into this disclosure. Technical Field

[0002] The present disclosure belongs to the field of biomedicine, and particularly relates to a drug combination for treating uterine malignant tumors. Background Art

[0003] Endometrial cancer (EC), also known as uterine corpus cancer, is a group of epithelial malignancies that arise in the endometrium. It is one of the three most common malignant tumors of the female reproductive tract. It primarily occurs in perimenopausal and postmenopausal women. With increasing life expectancy and changing lifestyles, the incidence of endometrial cancer has shown a steady upward trend over the past two decades, with younger patients becoming the most common malignant tumor of the female reproductive system. In Western countries, endometrial cancer ranks second most frequently among female reproductive tract malignancies after cervical cancer, accounting for approximately 20%-30% of all gynecological malignancies. In some developed cities, the incidence of endometrial cancer has reached the top position among gynecological malignancies. The recurrence rate after surgery for Stage I and Stage II patients is approximately 15%, with 50%-70% of recurrences being symptomatic. Most recurrences occur within three years of treatment. Recurrences confined to the vagina or pelvis can still respond well to treatment. Isolated vaginal recurrences with radiotherapy have a 5-year survival rate of 50%-70%.

[0004] In principle, the treatment of endometrial cancer is primarily surgical, supplemented by radiotherapy, medications, and hormone therapy. For nulliparous, estrogen-dependent, early-stage endometrial cancer, conservative treatment with progestins is often used to preserve fertility. For advanced-stage patients, appropriate chemotherapy is administered before surgery to reduce tumor size. Appropriate chemotherapy drug selection can significantly improve surgical resection rates. For metastatic endometrial cancer and postoperative recurrence, hormonal agents such as progestins, gonadotropin-releasing hormone analogs, and aromatase inhibitors are commonly used, along with chemotherapy drugs such as paclitaxel, carboplatin, and doxorubicin. With the emergence of chemotherapy resistance, targeted therapies such as pembrolizumab, avelumab, bevacizumab, sorafenib, and sunitinib have become increasingly important in improving the efficacy and prognosis of endometrial cancer. The standard first-line chemotherapy regimen for advanced or recurrent endometrial cancer is paclitaxel combined with carboplatin. Treatment options are very limited after failure of first-line chemotherapy, and the prognosis is poor. The objective response rate (ORR) of chemotherapy is 15-16%, and the ORR of bevacizumab treatment is only 13.5%.

[0005] Uterine sarcoma (US) refers to a primary malignant tumor arising from the mesenchymal tissue of the uterus. Its histopathological classification primarily includes uterine leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, and other rare types, such as uterine adenosarcoma, malignant perivascular epithelioid cell tumor, and rhabdomyosarcoma. Uterine sarcoma is the most common of these. Uterine sarcoma can spread directly, through lymphatic or hematogenous spread, and metastasize. Currently, there is no consensus on the optimal treatment for this disease.

[0006] Programmed death 1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1), form a pair of immune co-stimulatory factors. Under normal circumstances, PD-1 exerts important immune regulatory functions through its ligand PD-L1. Activation of the PD-1 / PD-L1 signaling pathway can lead to the formation of an immunosuppressive tumor immune microenvironment, allowing tumor cells to evade immune surveillance and killing. Blocking the PD-1 / PD-L1 signaling pathway can reverse this immunosuppressive tumor immune microenvironment and enhance endogenous anti-tumor immune responses.

[0007] Summary of the Invention

[0008] In one aspect, the present disclosure provides a drug combination for treating uterine malignancies, comprising: an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic agent. The uterine malignancy is endometrial cancer and / or uterine sarcoma. In some embodiments, the uterine malignancy is endometrial cancer. In other embodiments, the uterine malignancy is uterine sarcoma.

[0009] Furthermore, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain CDR1 region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 4, a heavy chain CDR2 region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 5, a heavy chain CDR3 region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 6, a light chain CDR1 region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 10, a light chain CDR2 region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 11, and a light chain CDR3 region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 12.

[0010] In some embodiments, the chemotherapy drugs include, but are not limited to, one or more of platinum-based anti-tumor drugs, taxane-based anti-tumor drugs, antimetabolite-based anti-tumor drugs, camptothecin-based anti-tumor drugs, nitrogen mustard-based anti-tumor drugs, anthracycline-based anti-tumor drugs, vinca alkaloid-based anti-tumor drugs, podophylloalkaloid-based anti-tumor drugs, and hormonal anti-tumor drugs. In some embodiments, the chemotherapy drugs are selected from one or more of platinum-based anti-tumor drugs, taxane-based anti-tumor drugs, anthracycline-based anti-tumor drugs, and antimetabolite-based anti-tumor drugs. In some embodiments, the chemotherapy drugs are platinum-based anti-tumor drugs and / or taxane-based anti-tumor drugs.

[0011] Furthermore, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin or satraplatin; preferably, the platinum anti-tumor drug is carboplatin and / or cisplatin; more preferably, the platinum anti-tumor drug is carboplatin.

[0012] Furthermore, the taxane anti-tumor drug is selected from one or more of paclitaxel, liposome paclitaxel, albumin-bound paclitaxel, and docetaxel; preferably, the taxane anti-tumor drug is paclitaxel and / or docetaxel and / or liposome paclitaxel; more preferably, the taxane anti-tumor drug is paclitaxel or docetaxel.

[0013] Furthermore, the anthracycline anti-tumor drug is selected from one or more of doxorubicin, liposome doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, daunorubicin, pixantrone, and liposomal doxorubicin; preferably, the anthracycline anti-tumor drug is doxorubicin.

[0014] Furthermore, the antimetabolite anti-tumor drug is selected from one or more of carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fluorouracil, doxifluridine, trifluridine, cytarabine, gemcitabine, azacitidine, ancitabine, mercaptopurine, fludarabine, methotrexate, and pemetrexed; preferably, the antimetabolite anti-tumor drug is gemcitabine.

[0015] In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and paclitaxel. In some embodiments, the chemotherapy drug is carboplatin and a taxane anti-tumor drug. In some embodiments, the chemotherapy drug is carboplatin and paclitaxel.

[0016] In other embodiments, the chemotherapy drug is an anthracycline anti-tumor drug. In other embodiments, the chemotherapy drug is doxorubicin.

[0017] In other embodiments, the chemotherapy drugs are taxane anti-tumor drugs and antimetabolite anti-tumor drugs. In other embodiments, the chemotherapy drugs are docetaxel and gemcitabine.

[0018] In some embodiments, the pharmaceutical combination further comprises anlotinib or a pharmaceutically acceptable salt thereof.

[0019] On the other hand, the present disclosure provides a drug combination for treating uterine malignancies, comprising a first drug combination and, optionally, a second drug combination. In some embodiments, the drug combination comprises the first drug combination administered to a patient in need thereof in a first treatment phase, and, optionally, the second drug combination administered to a patient in need thereof in a second treatment phase. In some embodiments, the first treatment phase comprises 1 to 14 treatment cycles, preferably 2 to 12 treatment cycles, further preferably 4 to 10 treatment cycles, for example: 4 to 10 treatment cycles, 5 to 10 treatment cycles, 6 to 10 treatment cycles, 4 to 9 treatment cycles, 5 to 9 treatment cycles, 6 to 9 treatment cycles, 4 to 8 treatment cycles, 5 to 8 treatment cycles, or 6 to 8 treatment cycles, most preferably 6 to 8 treatment cycles, for example: 6 treatment cycles, 7 treatment cycles, and / or 8 treatment cycles.

[0020] In some embodiments, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.

[0021] In some embodiments, the second treatment period is after the first treatment period. In some embodiments, the second treatment period continues from the end of the first treatment period until the patient loses clinical benefit, has unacceptable toxicity, is evaluated as disease progression, and / or the investigator deems it inappropriate to continue the medication.

[0022] In another aspect, the present disclosure provides a drug combination for treating uterine malignancies, comprising a first drug combination and, optionally, a second drug combination, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug. In some embodiments, the chemotherapy drug in the first drug combination is a platinum anti-tumor drug and a taxane anti-tumor drug. In some embodiments, the chemotherapy drug in the first drug combination is a platinum anti-tumor drug and paclitaxel. In some embodiments, the chemotherapy drug in the first drug combination is carboplatin and a taxane anti-tumor drug. In some embodiments, the chemotherapy drug in the first drug combination is carboplatin and paclitaxel.

[0023] In other embodiments, the chemotherapy drug in the first drug combination is an anthracycline anti-tumor drug. In other embodiments, the chemotherapy drug in the first drug combination is doxorubicin. In other embodiments, the chemotherapy drug in the first drug combination is a taxane anti-tumor drug and an antimetabolite anti-tumor drug. In other embodiments, the chemotherapy drugs in the first drug combination are docetaxel and gemcitabine.

[0024] In some embodiments, the first drug combination further includes anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, a chemotherapy drug and anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, carboplatin and anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, doxorubicin and anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, docetaxel, gemcitabine and anlotinib or a pharmaceutically acceptable salt thereof.

[0025] In some embodiments, the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof. In some embodiments, the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0026] In some specific embodiments, the drug combination includes a first drug combination administered to a patient in need during a first treatment phase, and a second drug combination administered to a patient in need during a second treatment phase, wherein the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel, and the second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof. In other specific embodiments, the drug combination includes a first drug combination administered to a patient in need during a first treatment phase, and a second drug combination administered to a patient in need during a second treatment phase, wherein the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, carboplatin, and paclitaxel, and the second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof. In other specific embodiments, the drug combination includes a first drug combination administered to a patient in need during the first treatment phase, and a second drug combination administered to a patient in need during the second treatment phase, wherein the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, and doxorubicin, and the second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof. In other specific embodiments, the drug combination includes a first drug combination administered to a patient in need during the first treatment phase, and a second drug combination administered to a patient in need during the second treatment phase, wherein the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, docetaxel and gemcitabine, and the second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0027] In some embodiments, the first drug combination or the second drug combination comprises 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof; in some embodiments, the first drug combination or the second drug combination comprises 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof; in some embodiments, the first drug combination or the second drug combination comprises 1200 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof.

[0028] In some embodiments, the first drug combination or the second drug combination includes 6-12 mg of anlotinib or a pharmaceutically acceptable salt thereof; in some embodiments, the first drug combination or the second drug combination includes 6 mg, 8 mg, 10 mg or 12 mg of anlotinib or a pharmaceutically acceptable salt thereof; in some embodiments, the first drug combination or the second drug combination includes 8 mg or 10 mg of anlotinib or a pharmaceutically acceptable salt thereof.

[0029] In some embodiments, the first or second drug combination comprises 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof, and 6-12 mg of anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first or second drug combination comprises 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof; and 6 mg, 8 mg, 10 mg, or 12 mg of anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first or second drug combination comprises 1200 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof; and 6 mg, 8 mg, 10 mg, or 12 mg of anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the first drug combination or the second drug combination includes 1200 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof; and 8 mg or 10 mg of anlotinib or a pharmaceutically acceptable salt thereof.

[0030] In some embodiments, the amount of the anti-PD-L1 antibody or antigen-binding fragment thereof in the first or second drug combination is a daily dose. In some embodiments, the amount of the anti-PD-L1 antibody or antigen-binding fragment thereof in the drug combination is a once-daily dose. In some embodiments, the amount of the anti-PD-L1 antibody or antigen-binding fragment thereof in the first or second drug combination is a uniform dose. In some embodiments, the amount of the anti-PD-L1 antibody or antigen-binding fragment thereof in the first or second drug combination is a dose for one treatment cycle, where each treatment cycle is 3 weeks.

[0031] In some embodiments, the content of anlotinib or a pharmaceutically acceptable salt thereof in the first drug combination or the second drug combination is a daily dose. In some embodiments, the content of anlotinib or a pharmaceutically acceptable salt thereof in the drug combination is a once-daily dose.

[0032] In some embodiments, the unit dose of the anti-PD-L1 antibody or antigen-binding fragment thereof is 10-1800 mg, 100-1500 mg, 100-1200 mg, 600-1200 mg, or 100-600 mg. In some embodiments, the unit dose of the anti-PD-L1 antibody or antigen-binding fragment thereof is about 10 mg, about 40 mg, about 80 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 320 mg, about 340 mg, about 360 mg, about 380 mg, about 400 mg, about 420 mg, about 440 mg, about 460 mg, about 480 mg, about 500 mg, about 520 mg, about 540 mg, about 560 mg, about 580 mg, about 600 mg, about 620 mg, about 640 mg, about 660 mg, about 680 mg. or about 1800 mg, or a range thereof. In some embodiments, the unit dose of the anti-PD-L1 antibody or antigen-binding fragment thereof is 100 mg and / or 600 mg.

[0033] In some embodiments, the unit dose of anlotinib or a pharmaceutically acceptable salt thereof is 6 mg, 8 mg, 10 mg and / or 12 mg.

[0034] In some embodiments, described drug combination further comprises pharmaceutically acceptable excipient.Herein, " excipient (excipient) " is used to describe any composition except active ingredient.The selection of excipient will depend on factors such as the efficacy of specific administration mode, excipient to solubility and stability and the properties of dosage form to a great extent.As used herein, " pharmaceutically acceptable excipient " includes but is not limited to carrier, excipient, diluent, filler, adhesive, disintegrant, solubilizing agent, stabilizer, coloring agent, flavoring, surfactant, emulsifier, buffer or encapsulating material.The consumption of every kind of excipient can change within the conventional range in this area.

[0035] In some embodiments, the present disclosure includes a pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug, wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof and the chemotherapeutic drug (such as paclitaxel and carboplatin, doxorubicin, or docetaxel and gemcitabine) are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially or intermittently. In some embodiments, the pharmaceutical combination includes a pharmaceutical composition comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising a chemotherapeutic drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine). In some embodiments, the present disclosure includes a pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug, which further includes anlotinib or a pharmaceutically acceptable salt thereof, wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof, the chemotherapeutic drug (such as paclitaxel and carboplatin, doxorubicin, or docetaxel and gemcitabine) and anlotinib or a pharmaceutically acceptable salt thereof are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially or intermittently. In some embodiments, the drug combination includes a pharmaceutical composition comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising a chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine), and a pharmaceutical composition comprising anlotinib or a pharmaceutically acceptable salt thereof. Furthermore, the drug combination of the present disclosure is packaged in the same kit, which also includes instructions for treating uterine malignancies.

[0036] On the other hand, the present disclosure provides a kit for treating uterine malignancies, comprising: an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine). In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment is contained in a first compartment, and the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) is contained in other compartments. Optionally, the number of compartments in the kit can be increased as appropriate depending on the type of chemotherapy drug, wherein the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug can be administered to a patient in need simultaneously, sequentially, or intermittently. In some embodiments, the kit for treating uterine malignancies described in the present disclosure further comprises anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment is contained in the first compartment, anlotinib or its pharmaceutically acceptable salt is contained in the second compartment, and the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) is contained in the other compartments. Optionally, the number of compartments in the kit can be increased as appropriate depending on the type of chemotherapy drug. The anti-PD-L1 antibody or its antigen-binding fragment, the chemotherapy drug, and anlotinib or its pharmaceutically acceptable salt can be administered to a patient in need simultaneously, sequentially, or intermittently. In some embodiments, the kit further comprises instructions for treating uterine malignancies.

[0037] In some embodiments, the kit comprises: a pharmaceutical composition comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising a chemotherapeutic drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine). In some embodiments, the kit comprises: a pharmaceutical composition comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising a chemotherapeutic drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine), and a pharmaceutical composition comprising anlotinib or a pharmaceutically acceptable salt thereof.

[0038] In other embodiments, each component of the pharmaceutical combination of the present disclosure (e.g., an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine); or an anti-PD-L1 antibody or an antigen-binding fragment thereof, a chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) and anlotinib or a pharmaceutically acceptable salt thereof) is separately packaged in a respective medicine kit, and the medicine kit further includes instructions for using the pharmaceutical combination of the present disclosure to treat uterine malignancies.

[0039] Each chemotherapy drug can be independently formulated into a suitable pharmaceutical composition, or some or all of them can be formulated together with pharmaceutically acceptable excipients to form a suitable pharmaceutical composition. Preferably, each chemotherapy drug can be independently formulated into a suitable pharmaceutical composition together with pharmaceutically acceptable excipients. For example, carboplatin, paclitaxel, doxorubicin, gemcitabine, and docetaxel can be independently formulated into a pharmaceutical composition suitable for injection (such as an injection solution or powder injection) together with pharmaceutically acceptable excipients.

[0040] Further, the kit of the present disclosure is a kit suitable for administration within a single treatment cycle (e.g., 3 weeks as a treatment cycle), comprising a pharmaceutical composition containing 600-2400 mg of an anti-PD-L1 antibody or its antigen-binding fragment. In some embodiments, the kit is a kit suitable for administration within a single treatment cycle (e.g., 3 weeks as a treatment cycle), comprising a pharmaceutical composition containing 600-2400 mg of an anti-PD-L1 antibody or its antigen-binding fragment, and a pharmaceutical composition containing 84-168 mg of anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks is a treatment cycle. In a preferred embodiment, every 3 weeks is a treatment cycle.

[0041] The dosage of the anti-PD-L1 antibody or antigen-binding fragment thereof can be determined based on the severity of the disease, the response to the disease, any treatment-related toxicities, and the patient's age and health status. For example, the daily dose of the anti-PD-L1 antibody or antigen-binding fragment thereof can be 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg; in some embodiments, the daily dose of the anti-PD-L1 antibody or antigen-binding fragment thereof can be 600, 800, 1000, 1200, 1400, 1600, 1800, 2000, 2200, or 2400 mg; in a preferred embodiment, the daily dose of the anti-PD-L1 antibody or antigen-binding fragment thereof can be 1200 mg. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered parenterally; in some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered intravenously.

[0042] The dosing regimen of the anti-PD-L1 antibody or antigen-binding fragment thereof can be determined comprehensively based on the drug's activity, toxicity, and patient tolerance. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle; in some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the dose of the anti-PD-L1 antibody or antigen-binding fragment thereof administered in each treatment cycle is 600-2400 mg; in some specific embodiments, the dose of the anti-PD-L1 antibody or antigen-binding fragment thereof administered in each treatment cycle is 1200 mg. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once every 3 weeks at a dose of 600-2400 mg each time. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once every 3 weeks at a dose of 1200 mg each time. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once on day 1 of each treatment cycle (e.g., 3 weeks as a treatment cycle), each time at a dose of 1200 mg. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once on day 1 of each treatment cycle (e.g., 3 weeks as a treatment cycle), each time at a dose of 1200 mg via intravenous administration.

[0043] Carboplatin is administered according to known dosing regimens (including dosage, route of administration, and dosing regimen). In some embodiments, carboplatin is administered every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle; in some embodiments, carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, carboplatin is administered at an AUC of 5 mg / mL / min, 3.75 mg / mL / min, or 2.5 mg / mL / min during each treatment cycle. In some embodiments, carboplatin is administered at an AUC of 5 mg / mL / min during each treatment cycle. In some embodiments, carboplatin is administered once every 3 weeks at an AUC of 5 mg / mL / min, 3.75 mg / mL / min, or 2.5 mg / mL / min. In some embodiments, carboplatin is administered once every 3 weeks at an AUC of 5 mg / mL / min. In some embodiments, carboplatin is administered parenterally; in some embodiments, carboplatin is administered intravenously. In some embodiments, carboplatin is administered once on day 1 of each treatment cycle (e.g., a 3-week treatment cycle) at an AUC of 5 mg / mL / min. In some embodiments, carboplatin is administered once on day 1 of each treatment cycle (e.g., a 3-week treatment cycle) at an AUC of 5 mg / mL / min.

[0044] Paclitaxel is administered according to known dosing regimens (including dosage, route of administration, and dosing schedule). In some embodiments, paclitaxel is administered every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle; in some embodiments, paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the dose of paclitaxel administered during each treatment cycle is 175 mg / m2, 131.25 mg / m2, or 87.5 mg / m2. In some embodiments, the dose of paclitaxel administered during each treatment cycle is 175 mg / m2. In some embodiments, paclitaxel is administered once every 3 weeks at a dose of 175 mg / m2, 131.25 mg / m2, or 87.5 mg / m2. In some embodiments, paclitaxel is administered once every 3 weeks at a dose of 175 mg / m2. In some embodiments, paclitaxel is administered parenterally; in some embodiments, paclitaxel is administered intravenously. In some embodiments, paclitaxel is administered once on day 1 of each treatment cycle (e.g., a 3-week treatment cycle) at a dose of 175 mg / m2. In some embodiments, paclitaxel is administered once on day 1 of each treatment cycle (e.g., a 3-week treatment cycle) at a dose of 175 mg / m2 intravenously.

[0045] Doxorubicin is administered according to known dosing regimens (including dosage, route of administration, and dosing regimen). In some embodiments, doxorubicin is administered every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle; in some embodiments, doxorubicin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the dose of doxorubicin administered in each treatment cycle is 60 mg / m2, 45 mg / m2, or 30 mg / m2. In some embodiments, the dose of doxorubicin administered in each treatment cycle is 60 mg / m2. In some embodiments, doxorubicin is administered once every 3 weeks at a dose of 60 mg / m2, 45 mg / m2, or 30 mg / m2 each time. In some embodiments, doxorubicin is administered once every 3 weeks at a dose of 60 mg / m2 each time. In some embodiments, doxorubicin is administered parenterally; in some embodiments, doxorubicin is administered intravenously. In some embodiments, doxorubicin is administered once on day 1 of each treatment cycle (e.g., 3 weeks as a treatment cycle), each time at a dose of 60 mg / m2. In some embodiments, doxorubicin is administered once on day 1 of each treatment cycle (e.g., 3 weeks as a treatment cycle), each time at a dose of 60 mg / m2 administered intravenously.

[0046] Gemcitabine is administered according to a known dosing regimen (including dosage, route of administration, and dosing regimen). In some embodiments, gemcitabine is administered every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle; in some embodiments, gemcitabine is administered twice every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the dose of gemcitabine administered in each treatment cycle is 1800 mg / m2, 1350 mg / m2, or 900 mg / m2. In some embodiments, the dose of gemcitabine administered in each treatment cycle is 1800 mg / m2. In some embodiments, gemcitabine is administered twice every 3 weeks, each time at a dose of 900 mg / m2, 67.5 mg / m2, or 450 mg / m2. In some embodiments, gemcitabine is administered twice every 3 weeks, each time at a dose of 900 mg / m2. In some embodiments, gemcitabine is administered parenterally; in some embodiments, gemcitabine is administered intravenously. In some embodiments, gemcitabine is administered once on day 1 and day 8 of each treatment cycle (e.g., 3 weeks as a treatment cycle), each time at a dose of 900 mg / m2. In some embodiments, gemcitabine is administered once on day 1 and day 8 of each treatment cycle (e.g., 3 weeks as a treatment cycle), each time at a dose of 900 mg / m2 via intravenous administration.

[0047] Docetaxel is administered according to known dosing regimens (including dosage, route of administration, and dosing schedule). In some embodiments, docetaxel is administered every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle; in some embodiments, docetaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the dose of docetaxel administered in each treatment cycle is 75 mg / m2, 56.25 mg / m2, or 37.5 mg / m2. In some embodiments, the dose of docetaxel administered in each treatment cycle is 75 mg / m2. In some embodiments, docetaxel is administered once every 3 weeks at a dose of 75 mg / m2, 56.25 mg / m2, or 37.5 mg / m2. In some embodiments, docetaxel is administered once every 3 weeks at a dose of 75 mg / m2. In some embodiments, docetaxel is administered parenterally; in some embodiments, docetaxel is administered intravenously. In some embodiments, docetaxel is administered once on day 8 of each treatment cycle (e.g., a 3-week treatment cycle) at a dose of 75 mg / m2. In some embodiments, docetaxel is administered once on day 8 of each treatment cycle (e.g., a 3-week treatment cycle) at a dose of 75 mg / m2 intravenously.

[0048] In some embodiments, anlotinib or a pharmaceutically acceptable salt thereof is administered once a week, every 2 weeks, every 3 weeks, or every 4 weeks as a treatment cycle. In some embodiments, anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 6 mg, 8 mg, 10 mg or 12 mg for 2 consecutive weeks and a 1-week rest regimen. In some embodiments, anlotinib or a pharmaceutically acceptable salt thereof is administered once a day on days 8 to 21 of each treatment cycle (e.g., 3 weeks as a treatment cycle), at a dose of 6 mg, 8 mg, 10 mg or 12 mg each time. In some embodiments, anlotinib or a pharmaceutically acceptable salt thereof is administered once a day on days 8 to 21 of each treatment cycle (e.g., 3 weeks as a treatment cycle), at a dose of 6 mg, 8 mg, 10 mg or 12 mg each time. In some embodiments, anlotinib or a pharmaceutically acceptable salt thereof is administered once a day on days 8 to 21 of each treatment cycle (e.g., 3 weeks as a treatment cycle), at a dose of 8 mg or 10 mg each time.

[0049] In some embodiments, the dosage regimen of the anti-PD-L1 antibody or its antigen-binding fragment, chemotherapy drug (such as paclitaxel and carboplatin, doxorubicin, or docetaxel and gemcitabine) and anlotinib or its pharmaceutically acceptable salt can be adjusted according to the severity of the disease, the response of the disease, any treatment-related toxicity, the age and health status of the patient. For example, every 9 weeks can be adjusted to a treatment cycle; for example, a treatment cycle of the anti-PD-L1 antibody or its antigen-binding fragment can be adjusted to 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, or 15 weeks; for example, a treatment cycle of anlotinib or its pharmaceutically acceptable salt can be adjusted to 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, or 9 weeks.

[0050] In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug described in the present disclosure includes a pharmaceutical composition comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising a chemotherapeutic drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine), wherein the pharmaceutical composition comprising the anti-PD-L1 antibody or an antigen-binding fragment thereof is prepared in a single dose or multiple dose form suitable for administering 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg of the anti-PD-L1 antibody or an antigen-binding fragment thereof to the patient each time. In some embodiments, the pharmaceutical composition comprising an anti-PD-L1 antibody or antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg of the anti-PD-L1 antibody or antigen-binding fragment thereof in the first administration. In some embodiments, the pharmaceutical composition comprising an anti-PD-L1 antibody or antigen-binding fragment thereof is prepared as a multiple dose form suitable for administering to a patient 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg of the anti-PD-L1 antibody or antigen-binding fragment thereof in each administration. In some embodiments, the pharmaceutical composition comprising an anti-PD-L1 antibody or antigen-binding fragment thereof is prepared in a multiple-dose form suitable for administering 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg of the anti-PD-L1 antibody or antigen-binding fragment thereof to a patient at the first administration. In some embodiments, the pharmaceutical composition comprising an anti-PD-L1 antibody or antigen-binding fragment thereof is prepared in a multiple-dose form suitable for administering 1200 mg of the anti-PD-L1 antibody or antigen-binding fragment thereof to a patient at each administration. In some embodiments, the pharmaceutical composition comprising an anti-PD-L1 antibody or antigen-binding fragment thereof is prepared in a multiple-dose form suitable for administering 1200 mg of the anti-PD-L1 antibody or antigen-binding fragment thereof to a patient at the first administration. In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug described in the present disclosure further comprises a pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof is prepared into a single dose form suitable for administering 6 mg, 8 mg, 10 mg and / or 12 mg of anlotinib or a pharmaceutically acceptable salt thereof to a patient per day.In some embodiments, the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof is prepared into a single dose form suitable for administering 8 mg and / or 10 mg of anlotinib or a pharmaceutically acceptable salt thereof to a patient per day.

[0051] In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic agent described herein comprises: a pharmaceutical composition containing 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof provided in multiple doses. In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic agent described herein comprises: a pharmaceutical composition containing 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof provided in multiple doses. In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug described in the present disclosure comprises: a pharmaceutical composition containing 1200 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof provided in a multiple-dose form. In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug described in the present disclosure comprises: a pharmaceutical composition containing an anti-PD-L1 antibody or an antigen-binding fragment thereof with a unit dose of 100 mg or 600 mg. In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug described in the present disclosure further comprises: a pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof with a unit dose of 8 mg, 10 mg and / or 12 mg.

[0052] Further, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug described in the present disclosure is a pharmaceutical combination suitable for administration within a single treatment cycle (e.g., a 3-week treatment cycle), including a pharmaceutical composition containing 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug described in the present disclosure is a pharmaceutical combination suitable for administration within a single treatment cycle (e.g., a 3-week treatment cycle), including a pharmaceutical composition containing 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination comprising an anti-PD-L1 antibody or its antigen-binding fragment and a chemotherapy drug described in the present disclosure is a drug combination suitable for administration within a single treatment cycle (e.g., a 3-week treatment cycle), including a pharmaceutical composition containing 1200 mg of an anti-PD-L1 antibody or its antigen-binding fragment. In some embodiments, the drug combination comprising an anti-PD-L1 antibody or its antigen-binding fragment and a chemotherapy drug described in the present disclosure further includes a pharmaceutical composition containing 84-168 mg or 112-140 mg of anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the drug combination comprising an anti-PD-L1 antibody or its antigen-binding fragment and a chemotherapy drug described in the present disclosure further includes a pharmaceutical composition containing 112 mg or 140 mg of anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks is a treatment cycle. In a preferred embodiment, every 3 weeks is a treatment cycle.

[0053] Furthermore, the pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug described herein further comprises anlotinib or a pharmaceutically acceptable salt thereof, wherein the weight ratio of the anti-PD-L1 antibody or an antigen-binding fragment thereof to anlotinib or a pharmaceutically acceptable salt thereof is (0.35-29):1, preferably (3.5-29):1, more preferably (3.5-14.5):1, and most preferably (7-14.5):1 or (8-11.5):1. The anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof can be packaged separately or together. Furthermore, anlotinib or a pharmaceutically acceptable salt thereof can be packaged in multiple aliquots (e.g., 2 aliquots, 7 aliquots, 14 aliquots, 28 aliquots, or more); and the anti-PD-L1 antibody or an antigen-binding fragment thereof can be packaged in a single aliquot or multiple aliquots (e.g., 1 aliquot, 2 aliquots, 4 aliquots, or more).

[0054] In yet another aspect, the present disclosure further provides the use of the drug combination of the present disclosure or the kit of the present disclosure in the preparation of a medicament for treating uterine malignant tumors. Alternatively, the present disclosure further provides a method for treating uterine malignant tumors, comprising administering an effective amount of the drug combination of the present disclosure or the kit of the present disclosure to a patient in need thereof. Alternatively, the present disclosure further provides the use of the drug combination of the present disclosure or the kit of the present disclosure for treating uterine malignant tumors. In some embodiments, the treatment is a first-line treatment for uterine malignant tumors. A first-line treatment refers to a position in the sequence in which a patient receives different drugs or other treatments, wherein the first-line treatment is the first or standard treatment. In some specific embodiments, the present disclosure further provides the use of the drug combination of the present disclosure or the kit of the present disclosure in the preparation of a medicament for the first-line treatment of uterine malignant tumors. Alternatively, the present disclosure further provides a method for the first-line treatment of uterine malignant tumors, comprising administering an effective amount of the drug combination of the present disclosure or the kit of the present disclosure to a patient in need thereof. Alternatively, the present disclosure further provides the use of the drug combination of the present disclosure or the kit of the present disclosure for the first-line treatment of uterine malignant tumors.

[0055] In some embodiments, in the uses or methods of the present disclosure, it comprises administering a therapeutically effective amount of an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug to a patient in need thereof. In some embodiments, in the uses or methods of the present disclosure, a first drug combination is administered to a patient in need thereof in a first treatment phase; and optionally, a second drug combination is administered to a patient in need thereof in a second treatment phase. In some embodiments, the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug. In some embodiments, the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, a chemotherapeutic drug, and anlotinib or a pharmaceutically acceptable salt thereof. In some embodiments, the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof. In some embodiments, the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0056] In some embodiments, the uses or methods of the present disclosure comprise administering a first drug combination to a patient in need thereof during a first treatment phase, and administering a second drug combination to a patient in need thereof during a second treatment phase, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug, and a taxane anti-tumor drug, and the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof. In some specific embodiments, the uses or methods of the present disclosure comprise administering a first drug combination to a patient in need thereof during a first treatment phase, and administering a second drug combination to a patient in need thereof during a second treatment phase, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel, and the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof.

[0057] In other embodiments, the uses or methods of the present disclosure comprise administering a first drug combination to a patient in need thereof in a first treatment phase, and administering a second drug combination to a patient in need thereof in a second treatment phase, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, a platinum-based anti-tumor drug, and a taxane-based anti-tumor drug, and the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof. In other specific embodiments, the uses or methods of the present disclosure comprise administering a first drug combination to a patient in need thereof in a first treatment phase, and administering a second drug combination to a patient in need thereof in a second treatment phase, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, carboplatin, and paclitaxel, and the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0058] In other embodiments, the uses or methods of the present disclosure include administering a first drug combination to a patient in need during a first treatment phase, and administering a second drug combination to a patient in need during a second treatment phase, wherein the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, and an anthracycline anti-tumor drug, and the second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof. In other specific embodiments, the uses or methods of the present disclosure include administering a first drug combination to a patient in need during a first treatment phase, and administering a second drug combination to a patient in need during a second treatment phase, wherein the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, and doxorubicin, and the second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0059] In other embodiments, in the uses or methods of the present disclosure, it comprises administering a first drug combination to a patient in need thereof in a first treatment stage, and administering a second drug combination to a patient in need thereof in a second treatment stage, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, a taxane anti-tumor drug, and an antimetabolite anti-tumor drug, and the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof. In other specific embodiments, in the uses or methods of the present disclosure, it comprises administering a first drug combination to a patient in need thereof in a first treatment stage, and administering a second drug combination to a patient in need thereof in a second treatment stage, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof, anlotinib or a pharmaceutically acceptable salt thereof, docetaxel and gemcitabine, and the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0060] In some embodiments, the first treatment phase comprises 1 to 14 treatment cycles, preferably 2 to 12 treatment cycles, further preferably 4 to 10 treatment cycles, for example: 4 to 10 treatment cycles, 5 to 10 treatment cycles, 6 to 10 treatment cycles, 4 to 9 treatment cycles, 5 to 9 treatment cycles, 6 to 9 treatment cycles, 4 to 8 treatment cycles, 5 to 8 treatment cycles, or 6 to 8 treatment cycles, most preferably 6 to 8 treatment cycles, for example: 6 treatment cycles, 7 treatment cycles, and / or 8 treatment cycles.

[0061] In some embodiments, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.

[0062] In some embodiments, the second treatment period is after the first treatment period. In some embodiments, the second treatment period continues from the end of the first treatment period until the patient loses clinical benefit, has unacceptable toxicity, is evaluated as disease progression, and / or the investigator deems it inappropriate to continue the medication.

[0063] Furthermore, the anti-PD-L1 antibody or its antigen-binding fragment, carboplatin and paclitaxel are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially or intermittently. Further, the anti-PD-L1 antibody or its antigen-binding fragment, carboplatin, paclitaxel and anlotinib or its pharmaceutically acceptable salt are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially or intermittently. Or the anti-PD-L1 antibody or its antigen-binding fragment, doxorubicin and anlotinib or its pharmaceutically acceptable salt are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially or intermittently. Or the anti-PD-L1 antibody or its antigen-binding fragment, docetaxel, gemcitabine and anlotinib or its pharmaceutically acceptable salt are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially or intermittently.

[0064] The uterine malignancy described in the present disclosure is endometrial cancer and / or uterine sarcoma. In some embodiments, the uterine malignancy is endometrial cancer. In other embodiments, the uterine malignancy is uterine sarcoma.

[0065] Anlotinib or its pharmaceutically acceptable salt

[0066] The chemical name of anlotinib is 1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl]cyclopropylamine, which has the structural formula (I):

[0067] As used in the present disclosure, anlotinib can be administered in the form of its free base or in the form of its pharmaceutically acceptable salt. Pharmaceutically acceptable salts of anlotinib include, but are not limited to, salts formed by anlotinib and an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, dodecylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, and stearic acid. In some embodiments, the pharmaceutically acceptable salt is hydrochloride and maleate. In some embodiments, the pharmaceutically acceptable salt is dihydrochloride.

[0068] The dosage of anlotinib or its pharmaceutically acceptable salts in the present disclosure, unless otherwise stated, is based on the molecular weight of anlotinib free base.

[0069] Anlotinib or a pharmaceutically acceptable salt thereof can be administered by a variety of routes, including gastrointestinal and parenteral routes, including but not limited to oral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, transbuccal, intranasal, inhalation, vaginal, intraocular, topical, subcutaneous, intrafatty, intraarticular, intraperitoneal, and intrathecal administration. In some specific embodiments, the administration is by oral administration.

[0070] The dosage of anlotinib or a pharmaceutically acceptable salt thereof can be determined based on the severity of the disease, the response of the disease, any treatment-related toxicity, the age and health status of the patient. For example, the daily dose of anlotinib or a pharmaceutically acceptable salt thereof may be 2 mg to 20 mg. In some embodiments, the daily dose of anlotinib or a pharmaceutically acceptable salt thereof may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16 mg. Anlotinib or a pharmaceutically acceptable salt thereof may be administered once or more daily. In some embodiments, anlotinib or a pharmaceutically acceptable salt thereof is administered once daily in the form of an oral solid formulation.

[0071] The dosage regimen of anlotinib or a pharmaceutically acceptable salt thereof can be comprehensively determined based on the activity, toxicity and patient tolerance of the drug. Preferably, anlotinib or a pharmaceutically acceptable salt thereof is administered in an intermittent manner. The intermittent administration includes a dosing period and a drug-free period. During the dosing period, anlotinib or a pharmaceutically acceptable salt thereof can be administered once or more per day. For example, the ratio of the dosing period to the drug-free period in days is 2:(0.5-5), 2:(0.5-3), 2:(0.5-2), or 2:(0.5-1). In some embodiments, the drug is administered for 2 consecutive weeks and then rested for 2 weeks. In some embodiments, the drug is administered for 2 consecutive weeks and then rested for 1 week. In some embodiments, the drug is administered for 5 consecutive days and then rested for 2 days. For example, anlotinib or a pharmaceutically acceptable salt thereof can be orally administered once daily at a dose of 6 mg, 8 mg, 10 mg or 12 mg for 2 consecutive weeks and then rested for 1 week. For example, anlotinib or a pharmaceutically acceptable salt thereof can be orally administered at a dose of 8 mg or 10 mg once daily for 2 consecutive weeks and then rest for 1 week.

[0072] Pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof

[0073] In some embodiments of the present disclosure, the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof is provided in the form of a single dose. In some embodiments, a single dose of the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof comprises 6 mg, 8 mg, 10 mg, or 12 mg of anlotinib.

[0074] In some embodiments of the present disclosure, the drug is administered according to a regimen of 2 weeks on and 1 week off, with each 3-week treatment cycle being a treatment cycle, and the total dose of anlotinib or a pharmaceutically acceptable salt thereof administered in each treatment cycle is 84-168 mg. In some embodiments, the drug is administered according to a regimen of 2 weeks on and 1 week off, with each 3-week treatment cycle being a treatment cycle, and the total dose of anlotinib or a pharmaceutically acceptable salt thereof administered in each treatment cycle includes 84 mg, 112 mg, 140 mg, 168 mg, or a range formed by any of the above values. In some embodiments, the drug is administered according to a regimen of 2 weeks on and 1 week off, with each 3-week treatment cycle being a treatment cycle, and the total dose of anlotinib or a pharmaceutically acceptable salt thereof administered in each treatment cycle includes 112 mg-140 mg.

[0075] In some embodiments, the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof includes but is not limited to preparations suitable for oral, parenteral, and topical administration; in some embodiments, the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof is a preparation suitable for oral administration, and the oral preparation can be prepared by conventional methods using pharmaceutically acceptable excipients known in the art; in some embodiments, the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof is a solid preparation suitable for oral administration; in some embodiments, the pharmaceutical composition containing anlotinib or a pharmaceutically acceptable salt thereof includes but is not limited to tablets and capsules. In a specific embodiment, the pharmaceutically acceptable excipients for the solid preparation suitable for oral administration include mannitol, microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate.

[0076] chemotherapy drugs

[0077] In some embodiments of the present disclosure, the chemotherapy drugs include but are not limited to platinum anti-tumor drugs (including but not limited to oxaliplatin, cisplatin, carboplatin, nedaplatin, dicycloplatin, miplatin, lobaplatin, picoplatin, levoplatin, triplatinum tetranitrate, phenanthreneplatin, satraplatin), camptothecin anti-tumor drugs (including but not limited to camptothecin, hydroxycamptothecin, aminocamptothecin, irinotecan, topotecan, exitecan, rubitecan, lurtotecan, gimatecan, karenitecin, 7-ethylcamptothecin), purple Taxane anti-tumor drugs (including but not limited to paclitaxel, liposome paclitaxel, albumin-bound paclitaxel and docetaxel), nitrogen mustard anti-tumor drugs (including but not limited to cyclophosphamide, ifosfamide, chlorambucil, carmustine, melphalan, bendamustine), antimetabolite anti-tumor drugs (including but not limited to fluorouracil anti-tumor drugs (including but not limited to carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fufuroxil, doxorubicin, trifluridine), cytosine anti-tumor drugs (including but not limited to cytarabine, gemcitabine, azacitidine, ancitabine), Purine anti-tumor drugs (including but not limited to mercaptopurine and fludarabine), anti-folate anti-tumor drugs (including but not limited to methotrexate and pemetrexed), anthracycline anti-tumor drugs (including but not limited to doxorubicin, liposomal doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, zorubicin, pixantrone, liposomal doxorubicin), vinca alkaloids (including but not limited to vinblastine, vincristine, vindesine, vinflunine and vinorelbine), podophyllotoxin One or more of: anti-tumor drugs (including but not limited to etoposide and teniposide), hormonal anti-tumor drugs (including but not limited to prednisone, prednisolone, dexamethasone, methylprednisolone sodium succinate), procarbazine, hexamethasone, dacarbazine, mitomycin, actinomycin D (dactinomycin), bleomycin, bleomycin, temozolomide, decamidine, peplomycin, eribulin, plinabulin, sapacitabine, treosulfan, 153Sm-EDTMP, and encequidar.

[0078] In some embodiments, the chemotherapy drug is selected from one or more of a platinum-based anti-tumor drug, a taxane-based anti-tumor drug, an anthracycline-based anti-tumor drug, and an antimetabolite-based anti-tumor drug. In some embodiments, the chemotherapy drug is a platinum-based anti-tumor drug and / or a taxane-based anti-tumor drug. In other embodiments, the chemotherapy drug is an anthracycline-based anti-tumor drug. In other embodiments, the chemotherapy drug is a taxane-based anti-tumor drug and / or an antimetabolite-based anti-tumor drug.

[0079] Furthermore, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin or satraplatin; preferably, the platinum anti-tumor drug is carboplatin and / or cisplatin; more preferably, the platinum anti-tumor drug is carboplatin.

[0080] Furthermore, the taxane anti-tumor drug is selected from one or more of paclitaxel, liposome paclitaxel, albumin-bound paclitaxel, and docetaxel; preferably, the taxane anti-tumor drug is paclitaxel and / or docetaxel and / or liposome paclitaxel; more preferably, the taxane anti-tumor drug is paclitaxel.

[0081] In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and paclitaxel. In some embodiments, the chemotherapy drug is carboplatin and a taxane anti-tumor drug. In some embodiments, the chemotherapy drug is carboplatin and paclitaxel.

[0082] Furthermore, the anthracycline anti-tumor drug is selected from one or more of doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, daunorubicin, pixantrone, and liposomal doxorubicin; preferably, the anthracycline anti-tumor drug is doxorubicin.

[0083] Furthermore, the antimetabolite anti-tumor drug is selected from one or more of carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fluorouracil, doxifluridine, trifluridine, cytarabine, gemcitabine, azacitidine, ancitabine, mercaptopurine, fludarabine, methotrexate, and pemetrexed; preferably, the antimetabolite anti-tumor drug is gemcitabine.

[0084] In other embodiments, the chemotherapy drug is an anthracycline anti-tumor drug. In other embodiments, the chemotherapy drug is doxorubicin.

[0085] In other embodiments, the chemotherapy drugs are taxane anti-tumor drugs and antimetabolite anti-tumor drugs. In other embodiments, the chemotherapy drugs are docetaxel and gemcitabine.

[0086] In the present disclosure, doxorubicin includes its non-salt form (e.g., free base) and its pharmaceutically acceptable salts, and both the non-salt form and the salt are included in the protection scope of the present disclosure. For example, the pharmaceutically acceptable salt of anlotinib can be hydrochloride.

[0087] In the present disclosure, gemcitabine includes its non-salt form (e.g., free base) and its pharmaceutically acceptable salt, and both the non-salt form and the salt are included in the protection scope of the present disclosure. For example, the pharmaceutically acceptable salt of gemcitabine can be hydrochloride.

[0088] In some embodiments, the chemotherapy drug is administered according to known administration methods (including dosage, route of administration, and dosing schedule).

[0089] Anti-PD-L1 antibody or antigen-binding fragment thereof

[0090] In some embodiments of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof is the anti-PD-L1 antibody or antigen-binding fragment thereof in WO2016022630 or CN107001463A.

[0091] In some embodiments of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof is an isolated anti-PD-L1 antibody or antigen-binding fragment thereof; in some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is an anti-PD-L1 humanized monoclonal antibody; in some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is an isolated anti-PD-L1 humanized monoclonal antibody; in some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof may be an IgG1 or IgG4 antibody; in some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is an IgG1 antibody.

[0092] In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain CDR1 region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) homologous to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 4; a heavy chain CDR2 region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) homologous to the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 5; NO:3 or SEQ ID NO:6, a heavy chain CDR3 region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous to the amino acid sequence of SEQ ID NO:7 or SEQ ID NO:10, a light chain CDR1 region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous to the amino acid sequence of SEQ ID NO:8 or SEQ ID NO:11, NO:11 has a light chain CDR2 region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous to the amino acid sequence of SEQ ID NO:11, and a light chain CDR3 region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous to the amino acid sequence of SEQ ID NO:9 or SEQ ID NO:12.

[0093] In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain CDR1 region selected from SEQ ID NO: 1 or SEQ ID NO: 4, a heavy chain CDR2 region selected from SEQ ID NO: 2 or SEQ ID NO: 5, a heavy chain CDR3 region selected from SEQ ID NO: 3 or SEQ ID NO: 6, a light chain CDR1 region selected from SEQ ID NO: 7 or SEQ ID NO: 10, a light chain CDR2 region selected from SEQ ID NO: 8 or SEQ ID NO: 11, and a light chain CDR3 region selected from SEQ ID NO: 9 or SEQ ID NO: 12. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain CDR1 region set forth in SEQ ID NO: 1, a heavy chain CDR2 region set forth in SEQ ID NO: 2, a heavy chain CDR3 region set forth in SEQ ID NO: 3, a light chain CDR1 region set forth in SEQ ID NO: 7, a light chain CDR2 region set forth in SEQ ID NO: 8, and a light chain CDR3 region set forth in SEQ ID NO: 9. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) homologous to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14, and a light chain variable region that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) homologous to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16.

[0094] In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region as set forth in SEQ ID NO: 13, and a light chain variable region as set forth in SEQ ID NO: 15. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region as set forth in SEQ ID NO: 14, and a light chain variable region as set forth in SEQ ID NO: 16.

[0095] In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous to the amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19 or SEQ ID NO: 21, and a heavy chain that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous to the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 21. The amino acid sequence shown in NO:20 has a light chain that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) homologous.

[0096] In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 17, and a light chain as set forth in SEQ ID NO: 18. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 19, and a light chain as set forth in SEQ ID NO: 20. In some embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 21, and a light chain as set forth in SEQ ID NO: 18.

[0097] In another embodiment, the anti-PD-L1 antibody or antigen-binding fragment thereof provided by the present disclosure may comprise a conservative substitution variant selected from one or more of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, and SEQ ID NO. 21. The anti-PD-L1 antibody or antigen-binding fragment thereof comprising the conservative substitution variant retains the ability to specifically recognize and bind to PD-L1.

[0098] In some embodiments of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof comprises a heavy chain complementary determining region (CDR) selected from 13C5 or 5G11 antibodies, and a light chain complementary determining region selected from 13C5 or 5G11 antibodies. In one embodiment, the anti-PD-L1 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region selected from ch5G11-hIgG1, ch5G11-hIgG4, ch13C5-hIgG1, ch13C5-hIgG4 chimeric antibodies, and a light chain variable region selected from ch5G11-hIgG1, ch5G11-hIgG4, ch13C5-hIgG1, ch13C5-hIgG4 chimeric antibodies. In one embodiment, the anti-PD-L1 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region selected from a humanized antibody hu13C5-hIgG1, hu13C5-hIgG4, hu5G11-hIgG1 or hu5G11-hIgG4, and a light chain variable region selected from a humanized antibody hu13C5-hIgG1, hu13C5-hIgG4, hu5G11-hIgG1 or hu5G11-hIgG4. Reference may be made to the records of patent documents WO2016022630 or CN107001463A: the HCDR1 sequence of 13C5, ch13C5-hIgG1, ch13C5-hIgG4, hu13C5-hIgG1 or hu13C5-hIgG4 is SYGMS (SEQ ID NO: 4), the HCDR2 sequence is SISSGGSTYYPDSVKG (SEQ ID NO: 5), the HCDR3 sequence is GYDSGFAY (SEQ ID NO: 6), the LCDR1 sequence is ASQSVSTSSSSFMH (SEQ ID NO: 10), the LCDR2 sequence is YASNLES (SEQ ID NO: 11), and the LCDR3 sequence is QHSWEIPYT (SEQ ID NO: 12). NO:12); the HCDR1 sequence of 5G11, ch5G11-hIgG1, ch5G11-hIgG4, hu5G11-hIgG1 or hu5G11-hIgG4 is TYGVH (SEQ ID NO:1), the HCDR2 sequence is VIWRGVTTDYNAAFMS (SEQ ID NO:2), the HCDR3 sequence is LGFYAMDY (SEQ ID NO:3), the LCDR1 sequence is KASQSVSNDVA (SEQ ID NO:7), the LCDR2 sequence is YAANRYT (SEQ ID NO:8), and the LCDR3 sequence is QQDYTSPYT (SEQ ID NO:9).

[0099] In other embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is atezolizumab, durvalumab, avelumab, envolimab (KN035), sugemalimab (CS1001), SHR-1316, socazolimab (ZKAB001), HS636, LP002, JS003, MSB2311, KL-A167 or STI-A1014.

[0100] In a preferred embodiment of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof is hu5G11-hIgG1, which comprises the heavy chain variable region amino acid sequence shown in SEQ ID NO: 13 and the light chain variable region amino acid sequence shown in SEQ ID NO: 15. In a preferred embodiment of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof is hu5G11-hIgG1, which comprises the heavy chain amino acid sequence shown in SEQ ID NO: 17 and the light chain amino acid sequence shown in SEQ ID NO: 18. In a preferred embodiment of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof is hu5G11-hIgG1, the heavy chain amino acid sequence of which is shown in SEQ ID NO: 17, and the light chain amino acid sequence of which is shown in SEQ ID NO: 18. In a preferred embodiment of the present disclosure, the anti-PD-L1 antibody is benmelstobart.

[0101] Pharmaceutical composition containing anti-PD-L1 antibody or antigen-binding fragment thereof

[0102] In some embodiments, the pharmaceutical composition containing the anti-PD-L1 antibody or antigen-binding fragment thereof can be in the form of multiple doses or a single dose.

[0103] In some embodiments, the pharmaceutical composition comprises 100 mg, 300 mg, 600 mg, or 1200 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof; in some embodiments, a pharmaceutical composition formulated as a single dose is provided, comprising 100 mg, 300 mg, 600 mg, or 1200 mg of an anti-PD-L1 antibody or an antigen-binding fragment thereof. In some embodiments, a single dose of the pharmaceutical composition comprising the anti-PD-L1 antibody or an antigen-binding fragment thereof comprises 100 mg, 300 mg, 600 mg, or 1200 mg of the anti-PD-L1 antibody or an antigen-binding fragment thereof.

[0104] In one embodiment, the pharmaceutical composition containing an anti-PD-L1 antibody or an antigen-binding fragment thereof is a solution for injection. In some embodiments, the pharmaceutical composition containing an anti-PD-L1 antibody or an antigen-binding fragment thereof is an aqueous solution for injection. In some embodiments, the aqueous solution for injection includes but is not limited to a water-soluble preparation that has not been lyophilized or a water-soluble preparation reconstituted with a lyophilized powder. In other embodiments, the pharmaceutical composition containing an anti-PD-L1 antibody or an antigen-binding fragment thereof is a lyophilized preparation. The lyophilized preparation refers to a preparation prepared by a lyophilization process of an aqueous solution, in which the substance is first frozen, and then the amount of solvent is reduced by sublimation (primary drying process), and then the amount of solvent is reduced by desorption (secondary drying process) until the amount of solvent is a value that no longer supports biological activity or chemical reaction. The lyophilized preparation of the present disclosure can also be dried by other methods known in the art, such as spray drying and bubble drying.

[0105] In some embodiments, the concentration of the anti-PD-L1 antibody or antigen-binding fragment thereof in the pharmaceutical composition comprising the anti-PD-L1 antibody or antigen-binding fragment thereof is 1-200 mg / mL, 2-150 mg / mL, 4.5-100 mg / mL, 5-80 mg / mL, 10-60 mg / mL, 10-50 mg / mL, or 10-30 mg / mL. In some specific embodiments, the concentration of the anti-PD-L1 antibody or antigen-binding fragment thereof is about 4.8 mg / mL, about 5 mg / mL, about 10 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, about 80 mg / mL, about 100 mg / mL, or about 120 mg / mL. In some embodiments, the concentration of the anti-PD-L1 antibody or antigen-binding fragment thereof is about 4.8 mg / mL. In some embodiments, the concentration of the anti-PD-L1 antibody or antigen-binding fragment thereof is about 10 mg / mL. In some embodiments, the concentration of the anti-PD-L1 antibody or antigen-binding fragment thereof is about 30 mg / mL. In some embodiments, the concentration of the anti-PD-L1 antibody or antigen-binding fragment thereof is about 60 mg / mL.

[0106] In some embodiments, the pharmaceutical composition comprising the anti-PD-L1 antibody or antigen-binding fragment thereof further comprises one or more of a buffer, an isotonicity regulator, a stabilizer, and / or a surfactant.

[0107] In some embodiments, the pharmaceutical composition containing the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: an anti-PD-L1 antibody or antigen-binding fragment thereof at a mass volume concentration of about 1-150 mg / mL, a 3-50 mM buffer, 2-150 mg / mL isotonicity regulator / stabilizer, and 0.01-0.8 mg / mL surfactant, and has a pH of about 4.5-6.8.

[0108] In a specific embodiment, the pharmaceutical composition containing the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: (a) an anti-PD-L1 antibody at a mass volume concentration of about 10 mg / mL or about 30 mg / mL, (b) sucrose at a mass volume concentration of about 80 mg / mL, (c) polysorbate 80 at a mass volume concentration of about 0.2 mg / mL, (d) histidine at a molar concentration of about 10 mM, and (e) optionally an appropriate amount of hydrochloric acid to adjust the pH of the composition to about 5.5.

[0109] In some embodiments, the pharmaceutical composition containing the anti-PD-L1 antibody or antigen-binding fragment thereof is hu5G11-hIgG1 injection with a specification of 100 mg / 10 mL or 600 mg / 20 mL.

[0110] Endometrial cancer

[0111] In some embodiments, the endometrial cancer includes endometrioid carcinoma, non-endometrioid carcinoma, and carcinosarcoma. In some embodiments, the endometrial cancer includes endometrioid carcinoma, serous carcinoma, clear cell carcinoma, undifferentiated and dedifferentiated endometrial carcinoma, mixed endometrial adenocarcinoma, and uterine carcinosarcoma.

[0112] In some embodiments of the present disclosure, the endometrial cancer is advanced, and / or recurrent, and / or metastatic endometrial cancer; in some embodiments, the endometrial cancer is advanced endometrial cancer; in some embodiments, the endometrial cancer is recurrent endometrial cancer; in some embodiments, the endometrial cancer is advanced and / or recurrent endometrial cancer; in some embodiments, the endometrial cancer is recurrent and / or metastatic endometrial cancer. In some embodiments, the endometrial cancer is recurrent and / or metastatic advanced endometrial cancer. In some embodiments, the endometrial cancer is stage III endometrial cancer. In some embodiments, the endometrial cancer is stage IV endometrial cancer. In some embodiments, the endometrial cancer is stage III or IV endometrial cancer. In some embodiments, the endometrial cancer is stage III or IV or recurrent endometrial cancer.

[0113] In some embodiments of the present disclosure, the patient with endometrial cancer has not previously received any anti-tumor treatment; in some embodiments, the patient with endometrial cancer has not previously received systemic anti-tumor treatment; in some embodiments, the patient with endometrial cancer has not previously received first-line systemic anti-tumor treatment.

[0114] In some embodiments of the present disclosure, the patient with endometrial cancer is not suitable for treatment other than systemic therapy.

[0115] In some embodiments, the patient with endometrial cancer is not suitable for surgical treatment and / or radical radiotherapy.

[0116] In some embodiments, the patient with endometrial cancer has previously received at least one treatment; in some embodiments, the patient with endometrial cancer has previously received surgical treatment; in some embodiments, the patient with endometrial cancer has previously received non-radical surgical treatment; in some embodiments, the patient with endometrial cancer has previously received adjuvant treatment; in some embodiments, the patient with endometrial cancer has previously received neoadjuvant treatment; in some embodiments, the patient with endometrial cancer has previously received adjuvant and / or neoadjuvant treatment; in some embodiments, the patient with endometrial cancer has previously received surgical treatment and adjuvant treatment; in some embodiments, the patient with endometrial cancer has previously received surgical treatment and neoadjuvant treatment; in some embodiments, The patient with endometrial cancer has previously received surgery and adjuvant and / or neoadjuvant therapy; in some embodiments, the patient with endometrial cancer has previously received radiotherapy; in some embodiments, the patient with endometrial cancer has previously received chemotherapy; in some embodiments, the patient with endometrial cancer has previously received radiotherapy and chemotherapy; in some embodiments, the patient with endometrial cancer has previously received non-radical surgery and still has residual disease visible on imaging; in some embodiments, the patient with endometrial cancer has previously received at least one treatment and the disease has recurred; in some embodiments, the patient with endometrial cancer has previously received surgery, or surgery combined with adjuvant therapy, or surgery combined with neoadjuvant therapy, or surgery combined with adjuvant therapy and neoadjuvant therapy and the disease has recurred. In some embodiments, the adjuvant or neoadjuvant therapy includes external beam radiotherapy (EBRT), vaginal broiler radiotherapy, concurrent chemoradiotherapy, chemotherapy, and sequential chemoradiotherapy. In some specific embodiments, the adjuvant or neoadjuvant therapy includes platinum-containing chemotherapy, platinum-containing chemotherapy concurrently with radiotherapy, and platinum-containing chemotherapy sequentially with radiotherapy. In some embodiments, the platinum agent includes but is not limited to cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, leucoplatin, triplatin tetranitrate, phenanthridineplatin, or satraplatin.In some embodiments, the endometrial cancer is advanced and / or recurrent endometrial cancer that has not previously received systemic anti-tumor treatment; in some embodiments, the endometrial cancer is advanced and / or recurrent endometrial cancer that has not previously received first-line systemic anti-tumor treatment; in some embodiments, the endometrial cancer is endometrial cancer that has not previously received first-line systemic anti-tumor treatment and is not suitable for other treatments other than systemic treatment; in some embodiments, the endometrial cancer is advanced and / or recurrent endometrial cancer that is not suitable for surgical treatment and / or radical radiotherapy; in some embodiments, the endometrial cancer is advanced and / or recurrent endometrial cancer that has not previously received first-line systemic anti-tumor treatment and is not suitable for surgical treatment and / or radical radiotherapy; in some embodiments, the endometrial cancer is stage III or IV or recurrent endometrial cancer that has not previously received first-line systemic anti-tumor treatment and is not suitable for other treatments other than systemic treatment; in some embodiments, the endometrial cancer is stage III or IV or recurrent endometrial cancer that has not previously received first-line systemic anti-tumor treatment and is not suitable for other treatments other than systemic treatment. In some embodiments, the endometrial cancer is stage III or stage IV or recurrent endometrial cancer that has not received first-line systemic anti-tumor treatment but has received surgical treatment and is not suitable for other treatments other than systemic treatment; In some embodiments, the endometrial cancer is stage III or stage IV endometrial cancer that has not received first-line systemic anti-tumor treatment but has received non-radical surgical treatment (for example, residual lesions after non-radical surgical treatment) and is not suitable for other treatments other than systemic treatment. In some embodiments, the endometrial cancer is a recurrent stage III or stage IV endometrial cancer that has not previously received first-line systemic anti-tumor treatment but has received surgery, or surgery combined with adjuvant therapy and / or neoadjuvant therapy, and is not suitable for other treatments other than systemic therapy; In some embodiments, the endometrial cancer is a recurrent stage III or stage IV endometrial cancer that has not previously received first-line systemic anti-tumor treatment but has received surgery, or surgery combined with adjuvant therapy and / or neoadjuvant therapy, and is not suitable for other treatments other than systemic therapy.

[0117] In some embodiments, the recurrence time of the recurrent endometrial cancer patient is greater than 12 months after the completion of initial treatment (e.g., surgery, or surgery combined with adjuvant therapy). In some embodiments, the recurrence time of the recurrent endometrial cancer patient is greater than 6 months after the completion of adjuvant therapy and / or neoadjuvant therapy. In some embodiments, the adjuvant therapy or neoadjuvant therapy includes external beam radiotherapy (EBRT), vaginal posterior loading radiotherapy, concurrent chemoradiotherapy, chemotherapy, and sequential chemoradiotherapy.

[0118] In some embodiments, the endometrial cancer is microsatellite instability endometrial cancer. In some embodiments, the endometrial cancer is microsatellite instability-high (MSI-H) endometrial cancer. In some embodiments, the endometrial cancer is microsatellite instability-low (MSI-L) endometrial cancer. In some embodiments, the endometrial cancer is microsatellite stability (MSS) endometrial cancer. In some embodiments, the endometrial cancer is MSS / MSI-L endometrial cancer.

[0119] In some embodiments, the endometrial cancer is mismatch repair deficient (dMMR) endometrial cancer. In some embodiments, the endometrial cancer is non-mismatch repair deficient (non-dMMR) endometrial cancer, including mismatch repair proficient (pMMR) endometrial cancer.

[0120] In the present disclosure, the endometrial cancer includes but is not limited to type I (estrogen-dependent) endometrial cancer or type II (estrogen-independent) endometrial cancer.

[0121] Uterine sarcoma

[0122] In some embodiments, the uterine sarcoma includes uterine leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma, malignant perivascular epithelial cell tumor and rhabdomyosarcoma. In some embodiments, the endometrial stromal sarcoma is a high-grade endometrial stromal sarcoma or a low-grade endometrial stromal sarcoma. In some embodiments, the uterine adenosarcoma is a uterine adenosarcoma with sarcoma overgrowth or a uterine adenosarcoma without sarcoma overgrowth. In some embodiments, the sarcoma overgrowth is defined as a pathology report indicating that the high-grade sarcomatoid component accounts for more than 25% of the total tumor volume. In some embodiments, the uterine sarcoma is estrogen receptor positive and progesterone receptor positive (ER + / PR + )Uterine sarcoma.

[0123] In some embodiments of the present disclosure, the uterine sarcoma is an advanced, and / or recurrent, and / or metastatic uterine sarcoma; in some embodiments, the uterine sarcoma is an advanced uterine sarcoma; in some embodiments, the uterine sarcoma is a recurrent uterine sarcoma; in some embodiments, the uterine sarcoma is an advanced and / or recurrent uterine sarcoma; in some embodiments, the uterine sarcoma is a recurrent and / or metastatic uterine sarcoma. In some embodiments, the uterine sarcoma is stage I, stage II, stage III, or stage IV uterine sarcoma.

[0124] In some embodiments of the present disclosure, the patient with uterine sarcoma has not previously received any anti-tumor treatment; in some embodiments, the patient with uterine sarcoma has not previously received systemic anti-tumor treatment; in some embodiments, the patient with uterine sarcoma has not previously received first-line systemic anti-tumor treatment.

[0125] In some embodiments of the present disclosure, the patient with uterine sarcoma is not suitable for treatment other than systemic therapy.

[0126] In some embodiments, the patient with uterine sarcoma is not suitable for surgical treatment and / or radical radiotherapy.

[0127] In some embodiments, the patient with uterine sarcoma has previously received at least one treatment; in some embodiments, the patient with uterine sarcoma has previously received surgical treatment; in some embodiments, the patient with uterine sarcoma has previously received non-radical surgical treatment; in some embodiments, the patient with uterine sarcoma has previously received adjuvant treatment; in some embodiments, the patient with uterine sarcoma has previously received neoadjuvant treatment; in some embodiments, the patient with uterine sarcoma has previously received adjuvant and / or neoadjuvant treatment; in some embodiments, the patient with uterine sarcoma has previously received surgical treatment and adjuvant treatment; in some embodiments, the patient with uterine sarcoma has previously received surgical treatment and neoadjuvant treatment; in some embodiments, The patient with uterine sarcoma has previously received surgery and adjuvant and / or neoadjuvant therapy; in some embodiments, the patient with uterine sarcoma has previously received radiotherapy; in some embodiments, the patient with uterine sarcoma has previously received chemotherapy; in some embodiments, the patient with uterine sarcoma has previously received radiotherapy and chemotherapy; in some embodiments, the patient with uterine sarcoma has previously received non-radical surgery and still has residual disease visible on imaging; in some embodiments, the patient with uterine sarcoma has previously received at least one treatment and the disease has recurred; in some embodiments, the patient with uterine sarcoma has previously received surgery, or surgery combined with adjuvant therapy, or surgery combined with neoadjuvant therapy, or surgery combined with adjuvant therapy and neoadjuvant therapy and the disease has recurred. In some embodiments, the adjuvant or neoadjuvant therapy includes external beam radiotherapy (EBRT), vaginal posterior loading radiotherapy, concurrent chemoradiotherapy, chemotherapy, and sequential chemoradiotherapy. In some specific embodiments, the adjuvant or neoadjuvant therapy includes platinum-based chemotherapy, platinum-based chemotherapy concurrent with radiotherapy, and platinum-based chemotherapy sequential with radiotherapy. In some embodiments, the platinum agent includes but is not limited to cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, leucoplatin, triplatin tetranitrate, phenanthridineplatin, or satraplatin.

[0128] In some embodiments, the uterine sarcoma is a uterine sarcoma that has not received first-line systemic anti-tumor treatment in the past; in some embodiments, the uterine sarcoma is a uterine sarcoma that has not received first-line systemic anti-tumor treatment in the past and is not suitable for other treatments except systemic treatment; in some embodiments, the uterine sarcoma is a uterine sarcoma that is not suitable for surgical treatment and / or radical radiotherapy; in some embodiments, the uterine sarcoma is a uterine sarcoma that has not received first-line systemic anti-tumor treatment in the past and is not suitable for surgical treatment and / or radical radiotherapy; in some embodiments, the uterine sarcoma is a uterine sarcoma that has not received first-line systemic anti-tumor treatment in the past and is not suitable for systemic treatment. Uterine leiomyosarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma with sarcoma overgrowth, malignant perivascular epithelial cell tumor, and rhabdomyosarcoma that have not been treated with other treatments other than first-line systemic anti-tumor therapy; in some embodiments, the uterine sarcoma is uterine leiomyosarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma with sarcoma overgrowth, malignant perivascular epithelial cell tumor, and rhabdomyosarcoma that have not received first-line systemic anti-tumor therapy before and are not suitable for surgical treatment and / or radical radiotherapy; in some embodiments, the uterine sarcoma is uterine leiomyosarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma with sarcoma overgrowth, malignant perivascular epithelial cell tumor, and rhabdomyosarcoma that have not received first-line systemic anti-tumor therapy before but have received surgical treatment and are not suitable for systemic systemic In some embodiments, the uterine sarcoma is a uterine sarcoma that has not received first-line systemic anti-tumor treatment but has received non-radical surgical treatment (for example, residual lesions after non-radical surgical treatment), and is not suitable for other treatments other than systemic treatment; In some embodiments, the uterine sarcoma is a uterine leiomyosarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma with sarcoma overgrowth, malignant vascular perisarcoma, that has not received first-line systemic anti-tumor treatment but has received non-radical surgical treatment (for example, residual lesions after non-radical surgical treatment), and is not suitable for other treatments other than systemic treatment. Epithelioid cell tumor and rhabdomyosarcoma; in some embodiments, the uterine sarcoma is a uterine sarcoma that has not received first-line systemic anti-tumor treatment but has received surgery, or surgery combined with adjuvant therapy and / or neoadjuvant therapy, and is not suitable for other treatments other than systemic treatment; in some embodiments, the uterine sarcoma is uterine leiomyosarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma with sarcoma overgrowth, malignant perivascular epithelial cell tumor and rhabdomyosarcoma that has not received first-line systemic anti-tumor treatment but has received surgery, or surgery combined with adjuvant therapy and / or neoadjuvant therapy, and is not suitable for other treatments other than systemic treatment.

[0129] In some embodiments, the uterine sarcoma is recurrent uterine leiomyosarcoma, high-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, uterine adenosarcoma with sarcoma overgrowth, malignant perivascular epithelial cell tumor and rhabdomyosarcoma. In some embodiments, the recurrence time of the recurrent uterine sarcoma patient is greater than 12 months after the end of initial treatment (e.g., surgery, or surgery combined with adjuvant therapy). In some embodiments, the recurrence time of the recurrent uterine sarcoma patient is greater than 6 months after the end of adjuvant therapy and / or neoadjuvant therapy. In some embodiments, the adjuvant therapy or neoadjuvant therapy includes external beam radiotherapy (EBRT), vaginal posterior loading radiotherapy, concurrent chemoradiotherapy, chemotherapy and sequential chemoradiotherapy.

[0130] In some embodiments, the patient with uterine sarcoma has previously received anti-estrogen therapy (e.g., failed treatment). In some embodiments, the uterine sarcoma is a uterine sarcoma that has failed anti-estrogen therapy. In some embodiments, the uterine sarcoma is a low-grade endometrial stromal sarcoma, adenosarcoma without sarcoma overgrowth, or ER endometrial sarcoma that has failed anti-estrogen therapy. + / PR + Uterine sarcoma. In some embodiments, the anti-estrogen therapy is a treatment method that blocks the binding of estrogen receptors to estrogen, inhibiting the proliferation of cancer cells caused by estrogen, thereby inhibiting the development and metastasis of cancer lesions.

[0131] Administration

[0132] The following does not limit the mode of administration of the disclosed pharmaceutical combination.

[0133] The components of the pharmaceutical combination of the present disclosure can be administered individually or in part or in whole in various suitable ways, including but not limited to oral or parenteral (intravenous, intramuscular, topical or subcutaneous) administration. In some embodiments, the components of the pharmaceutical combination of the present disclosure can be administered individually or in part or in whole or in whole or in oral or injection (e.g., intravenous or intraperitoneal injection).

[0134] The components of the pharmaceutical combination of the present invention can be formulated into suitable dosage forms independently, or some or all of them can be formulated together into suitable dosage forms, including but not limited to tablets, buccal tablets, pills, capsules (such as hard capsules, soft capsules, enteric-coated capsules, microcapsules), elixirs, granules, syrups, injections (intramuscular, intravenous, intraperitoneal injections), granules, emulsions, suspensions, solutions, dispersions and sustained-release preparations for oral or parenteral administration.

[0135] The components of the pharmaceutical combination of the present disclosure may each independently, or some or all of them may contain pharmaceutically acceptable excipients (including carriers and / or excipients).

[0136] Dosage regimen

[0137] In some embodiments of the present disclosure, the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) are each a pharmaceutical composition and can be administered simultaneously, sequentially, or intermittently. In some embodiments of the present disclosure, the anti-PD-L1 antibody or its antigen-binding fragment, the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) and anlotinib or a pharmaceutically acceptable salt thereof are each a pharmaceutical composition and can be administered simultaneously, sequentially, or intermittently.

[0138] In some embodiments of the present disclosure, the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) are each administered in an intermittent manner. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment, the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) and anlotinib or a pharmaceutically acceptable salt thereof are each administered in an intermittent manner. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) are administered in the same or different dosing regimens. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment, the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) and anlotinib or a pharmaceutically acceptable salt thereof are administered in the same or different dosing regimens. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) are administered in different dosing regimens. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment, the chemotherapy drug (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) and anlotinib or a pharmaceutically acceptable salt thereof are administered in different dosing regimens.

[0139] In some embodiments of the present disclosure, the anti-PD-L1 antibody or its antigen-binding fragment can be administered once a week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In a specific embodiment, the anti-PD-L1 antibody or its antigen-binding fragment is administered once every 3 weeks. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment is administered at a dose of 600-2400 mg, 1200-2400 mg, 1200-1800 mg, or 1800-2400 mg each time. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment is administered at a dose of 600 mg, 800 mg, 1000 mg, 1200 mg, 1400 mg, 1600 mg, 1800 mg, 2000 mg, 2200 mg, or 2400 mg each time. In some embodiments, the anti-PD-L1 antibody or its antigen-binding fragment is administered at a dose of 1200 mg each time.

[0140] In some embodiments of the present disclosure, the anlotinib or a pharmaceutically acceptable salt thereof is administered once a week, every two weeks, every three weeks, or every four weeks as a treatment cycle. In some embodiments, the anlotinib or a pharmaceutically acceptable salt thereof can be administered once a day at a dose of 6 mg, 8 mg, 10 mg, or 12 mg each time for two consecutive weeks, followed by a one-week rest. In this case, every three weeks is a treatment cycle.

[0141] In some embodiments of the present disclosure, the chemotherapy drugs (eg, carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) can be administered according to known administration methods.

[0142] In some embodiments of the present disclosure, the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug, and optionally anlotinib or a pharmaceutically acceptable salt thereof, respectively, have the same or different treatment cycles. In some specific embodiments, the anti-PD-L1 antibody or its antigen-binding fragment and the chemotherapy drug, and optionally anlotinib or a pharmaceutically acceptable salt thereof, have the same treatment cycle, for example, every 1 week, every 2 weeks, every 3 weeks or every 4 weeks is a treatment cycle. In some embodiments, every 3 weeks is a treatment cycle. In some embodiments of the present disclosure, the drug combination of the present disclosure, or the dosage regimen of the kit of the present disclosure, the dosage regimen includes a first treatment phase, optionally including a second treatment phase.

[0143] The dosage regimens described herein are applicable to the use in preparing a medicament for treating uterine malignancies, the methods for treating uterine malignancies, and the uses for treating uterine malignancies described herein. The uterine malignancies are endometrial cancer and / or uterine sarcoma. In some embodiments, the uterine malignancy is endometrial cancer. In other embodiments, the uterine malignancy is uterine sarcoma.

[0144] In some embodiments, the first treatment phase comprises 1 to 14 treatment cycles, preferably 2 to 12 treatment cycles, further preferably 4 to 10 treatment cycles, for example: 4 to 10 treatment cycles, 5 to 10 treatment cycles, 6 to 10 treatment cycles, 4 to 9 treatment cycles, 5 to 9 treatment cycles, 6 to 9 treatment cycles, 4 to 8 treatment cycles, 5 to 8 treatment cycles, or 6 to 8 treatment cycles, most preferably 6 to 8 treatment cycles, for example: 6 treatment cycles, 7 treatment cycles, and / or 8 treatment cycles.

[0145] In some embodiments, the second treatment phase is after the first treatment phase. In some embodiments of the present disclosure, the second treatment phase comprises 2 to 20 treatment cycles. In some embodiments, the second treatment phase is continued from the end of the first treatment phase until loss of clinical benefit, intolerable toxicity, disease progression as assessed by efficacy, and / or the investigator deems it inappropriate to continue the medication.

[0146] In some embodiments of the present disclosure, the treatment cycle is 14 to 42 days; in some embodiments, the treatment cycle is 14, 21, 28, 35, or 42 days; in some embodiments, the treatment cycle is 21 days. In some specific embodiments, the first treatment phase and the second treatment phase have the same treatment cycle. In some specific embodiments, the treatment cycle of the first treatment phase and the second treatment phase are both 21 days.

[0147] In some embodiments of the present disclosure, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered once on day 1, 2, 3, 4, 5, 6, or 7 of each treatment cycle, preferably once on day 1 of each treatment cycle.

[0148] In some embodiments of the present disclosure, anlotinib or a pharmaceutically acceptable salt thereof is continuously administered on days 1-7, 8-14, 1-14, or 8-21 of each treatment cycle, preferably on days 8-21 of each treatment cycle.

[0149] In some embodiments of the present disclosure, the chemotherapy drugs (e.g., carboplatin and paclitaxel, doxorubicin, or docetaxel and gemcitabine) are administered according to known modes of administration (including dosage, route of administration, and dosing regimen). In some embodiments, the carboplatin is administered once on day 1, 2, 3, 4, 5, 6, or 7 of each treatment cycle, preferably once on day 1 of each treatment cycle. In some embodiments, the paclitaxel is administered once on day 1, 2, 3, 4, 5, 6, or 7 of each treatment cycle, preferably once on day 1 of each treatment cycle. In some embodiments, the doxorubicin is administered once on day 1, 2, 3, 4, 5, 6, or 7 of each treatment cycle, preferably once on day 1 of each treatment cycle. In some embodiments, the docetaxel is administered once on day 1, 2, 3, 4, 5, 6, or 7 of each treatment cycle, preferably once on day 1 of each treatment cycle. In some embodiments, the docetaxel is administered once on day 1, 2, 3, 4, 5, 6, 7, or 8 of each treatment cycle, preferably once on day 8 of each treatment cycle. In some embodiments, the gemcitabine is administered twice on day 1, 2, 3, 4, 5, 6, 7, or 8 of each treatment cycle, preferably once on day 1 and day 8 of each treatment cycle.

[0150] The present disclosure provides a method for treating uterine malignancies, comprising administering a first drug combination to a patient in need thereof during a first treatment phase; and optionally, administering a second drug combination to the patient in need thereof during a second treatment phase. The present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a medicament for treating uterine malignancies, and the use thereof for treating uterine malignancies, the drug combination comprising the first drug combination administered to the patient in need thereof during the first treatment phase, and optionally, the second drug combination administered to the patient in need thereof during the second treatment phase.

[0151] The present disclosure provides a method for first-line treatment of uterine malignancies, comprising administering a first drug combination to a patient in need thereof during a first treatment phase; and optionally, administering a second drug combination to the patient in need thereof during a second treatment phase. The present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a medicament for first-line treatment of uterine malignancies and the use of the drug combination for first-line treatment of uterine malignancies, wherein the drug combination comprises the first drug combination administered to the patient in need thereof during the first treatment phase, and optionally, the second drug combination administered to the patient in need thereof during the second treatment phase.

[0152] The uterine malignancy described in the present disclosure is endometrial cancer and / or uterine sarcoma. In some embodiments, the uterine malignancy is endometrial cancer. In other embodiments, the uterine malignancy is uterine sarcoma.

[0153] In some embodiments, the dosing regimen of the first treatment phase comprises: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once a day on days 1-7 of each treatment cycle; 2) a platinum-based anti-tumor drug is administered once a day on days 1-7 of each treatment cycle; 3) a taxane-based anti-tumor drug is administered once a day on days 1-7 of each treatment cycle; and optionally, 4) anlotinib or a pharmaceutically acceptable salt thereof is administered once a day on days 8-21 of each treatment cycle.

[0154] In some embodiments, the dosing regimen of the first treatment phase comprises: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) a platinum-based anti-tumor drug is administered once on day 1 of each treatment cycle; and 3) a taxane-based anti-tumor drug is administered once on day 1 of each treatment cycle.

[0155] In some embodiments, the dosing regimen of the first treatment phase comprises: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) a platinum-based anti-tumor drug is administered once on day 1 of each treatment cycle; 3) a taxane-based anti-tumor drug is administered once on day 1 of each treatment cycle; and 4) anlotinib or a pharmaceutically acceptable salt thereof is administered once daily on days 8-21 of each treatment cycle.

[0156] In some embodiments, the dosing regimen of the first treatment phase comprises: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof administered once a day on days 1-7 of each treatment cycle; 2) carboplatin administered once a day on days 1-7 of each treatment cycle; 3) paclitaxel administered once a day on days 1-7 of each treatment cycle; and optionally, 4) anlotinib or a pharmaceutically acceptable salt thereof administered once a day on days 8-21 of each treatment cycle.

[0157] In some embodiments, the dosing regimen of the first treatment phase comprises: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) carboplatin is administered once on day 1 of each treatment cycle; and 3) paclitaxel is administered once on day 1 of each treatment cycle.

[0158] In some embodiments, the dosing regimen of the first treatment phase includes: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) carboplatin is administered once on day 1 of each treatment cycle; 3) paclitaxel is administered once on day 1 of each treatment cycle; 4) anlotinib or a pharmaceutically acceptable salt thereof is administered once daily on days 8-21 of each treatment cycle.

[0159] In some embodiments, the dosing regimen of the first treatment phase comprises: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle. In some embodiments, the dosing regimen of the first treatment phase comprises: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0160] In other embodiments, the dosing regimen of the first treatment phase includes: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on the first day of each treatment cycle; 2) an anthracycline anti-tumor drug is administered once on the first day of each treatment cycle; 3) anlotinib or a pharmaceutically acceptable salt thereof is administered once a day on days 8-21 of each treatment cycle.

[0161] In some embodiments, the dosing regimen of the first treatment phase includes: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) a taxane anti-tumor drug is administered once on day 8 of each treatment cycle; 3) an antimetabolite anti-tumor drug is administered once on day 1 and day 8 of each treatment cycle; 4) anlotinib or a pharmaceutically acceptable salt thereof is administered once daily on days 8-21 of each treatment cycle.

[0162] In other embodiments, the dosing regimen of the first treatment phase includes: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) doxorubicin is administered once on day 1 of each treatment cycle; 3) anlotinib or a pharmaceutically acceptable salt thereof is administered once a day on days 8-21 of each treatment cycle.

[0163] In some embodiments, the dosing regimen of the first treatment phase includes: 1) an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle; 2) docetaxel is administered once on day 8 of each treatment cycle; 3) gemcitabine is administered once on day 1 and day 8 of each treatment cycle; 4) anlotinib or a pharmaceutically acceptable salt thereof is administered once daily on days 8-21 of each treatment cycle.

[0164] In some embodiments, the dosing regimen of the second treatment phase comprises administering the anti-PD-L1 antibody or antigen-binding fragment thereof once a day on days 1-7 of each treatment cycle. In some embodiments, the dosing regimen of the second treatment phase comprises administering the anti-PD-L1 antibody or antigen-binding fragment thereof once on day 1 of each treatment cycle.

[0165] In some embodiments, the dosing regimen of the second treatment phase comprises: 1) administering the anti-PD-L1 antibody or its antigen-binding fragment once a day on days 1-7 of each treatment cycle; and 2) administering anlotinib or a pharmaceutically acceptable salt thereof once a day on days 8-21 of each treatment cycle.

[0166] In some embodiments, the dosing regimen of the second treatment phase comprises: 1) administering the anti-PD-L1 antibody or its antigen-binding fragment once on day 1 of each treatment cycle; and 2) administering anlotinib or a pharmaceutically acceptable salt thereof once daily on days 8-21 of each treatment cycle.

[0167] In some embodiments, in the methods or uses of the present disclosure, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), paclitaxel, and carboplatin are administered to a patient in need thereof in a first treatment phase, and an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) is administered to a patient in need thereof in a second treatment phase, wherein the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0168] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle;

[0169] The dosing regimen of the second treatment phase includes administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle.

[0170] In some embodiments, in the methods or uses of the present disclosure, in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), paclitaxel, carboplatin, and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof; in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof; the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0171] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle;

[0172] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0173] In some embodiments, in the methods or uses of the present disclosure, in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), doxorubicin, and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0174] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof and doxorubicin on day 1 of each treatment cycle; administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle;

[0175] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0176] In some embodiments, in the methods or uses of the present disclosure, in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), gemcitabine, docetaxel, and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0177] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, gemcitabine, and docetaxel on day 1 of each treatment cycle; administering gemcitabine on day 8 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily from day 8 to day 21 of each treatment cycle.

[0178] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0179] In some embodiments, in the methods or uses of the present disclosure, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), paclitaxel, and carboplatin are administered to a patient in need thereof in a first treatment phase, and an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) is administered to a patient in need thereof in a second treatment phase, wherein the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0180] The dosing regimen of the first treatment phase includes: administering anti-PD-L1 antibody or its antigen-binding fragment, paclitaxel and carboplatin on day 1 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and paclitaxel is administered at a daily dose of 175 mg / m 2 , carboplatin was administered at a daily dose of 5 mg / mL / min AUC;

[0181] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; wherein the anti-PD-L1 antibody or an antigen-binding fragment thereof is administered at a daily dose of 1200 mg.

[0182] In some embodiments, in the methods or uses of the present disclosure, in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), paclitaxel, carboplatin, and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof; in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof; the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0183] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or its antigen-binding fragment, paclitaxel, and carboplatin on day 1 of each treatment cycle; administering anlotinib or its pharmaceutically acceptable salt daily on days 8-21 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and paclitaxel is administered at a daily dose of 175 mg / m 2 Carboplatin is administered at a daily dose of 5 mg / mL / min AUC, and anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 8 mg;

[0184] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; administering anlotinib or a pharmaceutically acceptable salt thereof daily from day 8 to day 21 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 10 mg.

[0185] In some embodiments, in the methods or uses of the present disclosure, in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), doxorubicin, and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0186] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or its antigen-binding fragment and doxorubicin on day 1 of each treatment cycle; administering anlotinib or its pharmaceutically acceptable salt daily on days 8-21 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and doxorubicin is administered at a daily dose of 60 mg / m 2 Anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 8 mg;

[0187] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; administering anlotinib or a pharmaceutically acceptable salt thereof daily from day 8 to day 21 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 10 mg.

[0188] In some embodiments, in the methods or uses of the present disclosure, in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1), gemcitabine, docetaxel, and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof (e.g., hu5G11-hIgG1) and anlotinib, or a pharmaceutically acceptable salt thereof, is administered to a patient in need thereof; the first treatment phase comprises 6 to 8 treatment cycles, with one treatment cycle consisting of 3 weeks.

[0189] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or its antigen-binding fragment, gemcitabine, and docetaxel on day 1 of each treatment cycle; administering gemcitabine on day 8 of each treatment cycle; and administering anlotinib or its pharmaceutically acceptable salt daily from day 8 to day 21 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and gemcitabine is administered at a daily dose of 900 mg / m 2 Docetaxel was given at a daily dose of 75 mg / m 2 Anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 8 mg;

[0190] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; administering anlotinib or a pharmaceutically acceptable salt thereof daily from day 8 to day 21 of each treatment cycle; wherein the anti-PD-L1 antibody or its antigen-binding fragment is administered at a daily dose of 1200 mg, and anlotinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 10 mg.

[0191] In some embodiments, the second treatment period is after the first treatment period. In some embodiments, the second treatment period continues from the end of the first treatment period until the patient loses clinical benefit, has unacceptable toxicity, is evaluated as disease progression, and / or the investigator deems it inappropriate to continue the medication.

[0192] In some embodiments, the treatment is a first-line treatment for a uterine malignancy. In some embodiments, the uterine malignancy is endometrial cancer and / or uterine sarcoma. In some embodiments, the uterine malignancy is endometrial cancer. In other embodiments, the uterine malignancy is a uterine sarcoma.

[0193] The present disclosure also provides the following specific implementation schemes, but the protection scope of the present disclosure is not limited thereto:

[0194] Embodiment 1. A pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug for treating uterine malignancies, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain CDR1 region as shown in SEQ ID NO: 1, a heavy chain CDR2 region as shown in SEQ ID NO: 2, a heavy chain CDR3 region as shown in SEQ ID NO: 3, a light chain CDR1 region as shown in SEQ ID NO: 7, a light chain CDR2 region as shown in SEQ ID NO: 8, and a light chain CDR3 region as shown in SEQ ID NO: 9.

[0195] Embodiment 2. The use according to embodiment 1, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region that is at least 80% homologous to the amino acid sequence shown in SEQ ID NO: 13, and a light chain variable region that is at least 80% homologous to the amino acid sequence shown in SEQ ID NO: 15.

[0196] Embodiment 3. The use according to embodiment 1 or 2, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain having at least 80% homology to the amino acid sequence shown in SEQ ID NO: 17, and a light chain having at least 80% homology to the amino acid sequence shown in SEQ ID NO: 18.

[0197] Embodiment 4. The use according to any one of Embodiments 1-3, wherein the drug combination further comprises anlotinib or a pharmaceutically acceptable salt thereof.

[0198] Embodiment 5. The use according to any one of Embodiments 1-4, wherein the drug combination comprises a first drug combination, and optionally, a second drug combination; the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug.

[0199] Embodiment 6. The use according to embodiment 5, wherein the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof.

[0200] Embodiment 7. The use according to embodiment 5, wherein the first drug combination further comprises anlotinib or a pharmaceutically acceptable salt thereof.

[0201] Embodiment 8. The use according to embodiment 7, wherein the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0202] Embodiment 9. The use according to any one of embodiments 5-8, wherein the first drug combination is administered to a patient in need thereof in a first treatment phase, and optionally, the second drug combination is administered to a patient in need thereof in a second treatment phase; the first treatment phase comprises 1 to 14 treatment cycles, 2 to 12 treatment cycles, preferably 4 to 10 treatment cycles, and most preferably 6 to 8 treatment cycles.

[0203] Embodiment 10. The use according to embodiment 9, wherein one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably every 3 weeks.

[0204] Embodiment 11. The use according to any one of Embodiments 1-10, wherein the chemotherapy drug is selected from one or more of platinum anti-tumor drugs, taxane anti-tumor drugs, anthracycline anti-tumor drugs, and antimetabolite anti-tumor drugs;

[0205] Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenanthreneplatin, and satraplatin;

[0206] Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, liposome paclitaxel, albumin-bound paclitaxel, and docetaxel;

[0207] Optionally, the anthracycline anti-tumor drug is selected from one or more of doxorubicin, liposome doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, daunorubicin, pixantrone, and liposomal doxorubicin;

[0208] Optionally, the antimetabolite anti-tumor drug is selected from one or more of carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fluorouracil, doxifluridine, trifluridine, cytarabine, gemcitabine, azacitidine, ancitabine, mercaptopurine, fludarabine, methotrexate, and pemetrexed.

[0209] Embodiment 12. The use according to any one of Embodiments 1-11, wherein the chemotherapy drug is selected from carboplatin and paclitaxel, or the chemotherapy drug is selected from doxorubicin, or the chemotherapy drug is selected from docetaxel and gemcitabine.

[0210] Embodiment 13. The use according to embodiment 12, wherein in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin are administered to a patient in need thereof, and in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered to a patient in need thereof, wherein the first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks being one treatment cycle;

[0211] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle;

[0212] The dosing regimen of the second treatment phase includes administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle.

[0213] Embodiment 14. The use according to embodiment 12, wherein in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, carboplatin, and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof, and in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof, wherein the first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks being one treatment cycle;

[0214] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle;

[0215] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0216] Embodiment 15. The use according to embodiment 12, wherein in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, doxorubicin, and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof, and in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof, wherein the first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks being one treatment cycle;

[0217] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof and doxorubicin on day 1 of each treatment cycle; administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle;

[0218] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0219] Embodiment 16. The use according to embodiment 12, wherein in a first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, gemcitabine, docetaxel, and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof, and in a second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof are administered to a patient in need thereof, wherein the first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks being one treatment cycle;

[0220] The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, gemcitabine, and docetaxel on day 1 of each treatment cycle; administering gemcitabine on day 8 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily from day 8 to day 21 of each treatment cycle.

[0221] The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

[0222] Embodiment 17. The use according to any one of embodiments 1 to 16, wherein the uterine malignancy is endometrial cancer or uterine sarcoma.

[0223] Embodiment 18. The use according to any one of embodiments 1 to 17, wherein the treatment is first-line treatment for endometrial cancer or uterine sarcoma.

[0224] Embodiment 19. The use according to embodiment 17 or 18, wherein the endometrial cancer is advanced, recurrent, and / or metastatic endometrial cancer, or the endometrial cancer is stage III or stage IV or recurrent endometrial cancer.

[0225] Embodiment 20. The use according to any one of Embodiments 17 to 19, wherein the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has not previously received first-line systemic anti-tumor treatment, and / or an endometrial cancer or uterine sarcoma that is not suitable for treatment other than systemic treatment.

[0226] Embodiment 21. The use according to any one of Embodiments 17-20, wherein the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has previously received non-radical surgical treatment, or the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has previously received at least one treatment and the disease has recurred, or the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has previously received surgery, or surgery combined with adjuvant therapy and / or neoadjuvant therapy and the disease has recurred.

[0227] Embodiment 22. The use according to any one of embodiments 17-21, wherein the endometrial cancer is microsatellite instability endometrial cancer, high microsatellite instability (MSI-H) endometrial cancer, low microsatellite instability (MSI-L) endometrial cancer, microsatellite stability (MSS) endometrial cancer, MSS / MSI-L endometrial cancer, mismatch repair deficient (dMMR) endometrial cancer, or non-mismatch repair deficient (non-dMMR) endometrial cancer.

[0228] Embodiment 23. A drug combination for treating uterine malignancies, comprising: an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain CDR1 region as shown in SEQ ID NO: 1, a heavy chain CDR2 region as shown in SEQ ID NO: 2, a heavy chain CDR3 region as shown in SEQ ID NO: 3, a light chain CDR1 region as shown in SEQ ID NO: 7, a light chain CDR2 region as shown in SEQ ID NO: 8, and a light chain CDR3 region as shown in SEQ ID NO: 9.

[0229] Embodiment 24. The drug combination according to Embodiment 23, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain variable region that is at least 80% homologous to the amino acid sequence shown in SEQ ID NO: 13, and a light chain variable region that is at least 80% homologous to the amino acid sequence shown in SEQ ID NO: 15.

[0230] Embodiment 25. The pharmaceutical combination of embodiment 23 or 24, wherein the anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain having at least 80% homology to the amino acid sequence shown in SEQ ID NO: 17, and a light chain having at least 80% homology to the amino acid sequence shown in SEQ ID NO: 18.

[0231] Embodiment 26. The pharmaceutical combination according to any one of Embodiments 23-25, wherein the pharmaceutical combination further comprises anlotinib or a pharmaceutically acceptable salt thereof.

[0232] Embodiment 27. The drug combination according to any one of Embodiments 23-26, wherein the drug combination comprises a first drug combination and, optionally, a second drug combination, wherein the first drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug.

[0233] Embodiment 28. The drug combination according to embodiment 27, wherein the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof.

[0234] Embodiment 29. The drug combination according to Embodiment 27, wherein the first drug combination further comprises anlotinib or a pharmaceutically acceptable salt thereof.

[0235] Embodiment 30. The drug combination according to Embodiment 29, wherein the second drug combination comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

[0236] Embodiment 31. The drug combination according to any one of embodiments 27-30, wherein the first drug combination is administered to a patient in need thereof in a first treatment phase, and optionally, the second drug combination is administered to a patient in need thereof in a second treatment phase; the first treatment phase comprises 1 to 14 treatment cycles, 2 to 12 treatment cycles, preferably 4 to 10 treatment cycles, and most preferably 6 to 8 treatment cycles.

[0237] Embodiment 32. The pharmaceutical combination according to embodiment 31, wherein one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably every 3 weeks.

[0238] Embodiment 33. The drug combination according to any one of Embodiments 23-32, wherein the chemotherapy drug is selected from one or more of platinum anti-tumor drugs, taxane anti-tumor drugs, anthracycline anti-tumor drugs, and antimetabolite anti-tumor drugs;

[0239] Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenanthreneplatin, and satraplatin;

[0240] Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, liposome paclitaxel, albumin-bound paclitaxel, and docetaxel;

[0241] Optionally, the anthracycline anti-tumor drug is selected from one or more of doxorubicin, liposome doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, daunorubicin, pixantrone, and liposomal doxorubicin;

[0242] Optionally, the antimetabolite anti-tumor drug is selected from one or more of carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fluorouracil, doxifluridine, trifluridine, cytarabine, gemcitabine, azacitidine, ancitabine, mercaptopurine, fludarabine, methotrexate, and pemetrexed.

[0243] Embodiment 34. The drug combination according to any one of Embodiments 23-33, wherein the chemotherapy drug is selected from carboplatin and paclitaxel, or the chemotherapy drug is selected from doxorubicin, or the chemotherapy drug is selected from docetaxel and gemcitabine.

[0244] Embodiment 35. The pharmaceutical combination according to any one of embodiments 23-34, wherein the uterine malignancy is endometrial cancer or uterine sarcoma.

[0245] Embodiment 36. The pharmaceutical combination according to any one of embodiments 23 to 35, wherein the treatment is first-line treatment for endometrial cancer or uterine sarcoma.

[0246] Embodiment 37. The pharmaceutical combination according to embodiment 35 or 36, wherein the endometrial cancer is advanced, recurrent, and / or metastatic endometrial cancer, or the endometrial cancer is stage III or stage IV or recurrent endometrial cancer.

[0247] Embodiment 38. The drug combination according to any one of Embodiments 35-37, wherein the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has not previously received first-line systemic anti-tumor treatment, and / or an endometrial cancer or uterine sarcoma that is not suitable for treatment other than systemic treatment.

[0248] Embodiment 39. The drug combination according to any one of Embodiments 35-38, wherein the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has previously received non-radical surgical treatment, or the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has recurred after previously receiving at least one treatment, or the endometrial cancer or uterine sarcoma is an endometrial cancer or uterine sarcoma that has recurred after previously receiving surgery, or surgery combined with adjuvant therapy and / or neoadjuvant therapy.

[0249] Embodiment 40. The drug combination according to any one of embodiments 35-39, wherein the endometrial cancer is microsatellite instability endometrial cancer, high microsatellite instability (MSI-H) endometrial cancer, low microsatellite instability (MSI-L) endometrial cancer, microsatellite stable (MSS) endometrial cancer, MSS / MSI-L endometrial cancer, mismatch repair deficient (dMMR) endometrial cancer, or non-mismatch repair deficient (non-dMMR) endometrial cancer.

[0250] Technical Effects

[0251] Generally, the drug combinations disclosed herein have one or more of the following effects: (1) better efficacy in reducing tumor growth or even eliminating tumors compared to administration of any of the drugs in the combination alone; (2) providing a smaller dosage compared to administration of any of the drugs in the combination alone; (3) well-tolerated treatment in patients with fewer adverse reactions and / or complications compared to administration of any of the drugs alone; (4) better disease control rates among treated patients; (5) longer survival (e.g., median survival, progression-free survival, or overall survival) in treated patients; (6) longer survival (e.g., median survival, progression-free survival, or overall survival) in treated patients compared to standard chemotherapy; (7) longer duration of disease remission (DOR); and / or (8) good activity in treating tumors or proliferative diseases, showing a superior anti-tumor synergistic effect, compared to administration of any of the drugs in the combination alone.

[0252] The drug combination and treatment regimen disclosed herein have good efficacy in the treatment of uterine malignancies, and have beneficial effects on at least one of ORR, DCR, DoR, PFS, OS, tolerability, and side effects.

[0253] The present disclosure provides a drug combination comprising hu5G11-hIgG1, carboplatin, and paclitaxel for safe and effective treatment of uterine malignancies. Patients with uterine malignancies experience beneficial effects in at least one of ORR, DCR, DOR, PFS, OS, tolerability, and side effects following treatment with a regimen comprising administering hu5G11-hIgG1, carboplatin, and paclitaxel to the patient in a first treatment phase and administering hu5G11-hIgG1 to the patient in a second treatment phase.

[0254] The present disclosure provides a drug combination comprising hu5G11-hIgG1, carboplatin, paclitaxel, and anlotinib hydrochloride that can safely and effectively treat uterine malignancies. Patients with uterine malignancies experience beneficial effects in at least one of ORR, DCR, DOR, PFS, OS, tolerability, and side effects after receiving a treatment regimen comprising administering hu5G11-hIgG1, carboplatin, paclitaxel, and anlotinib hydrochloride to the patient in a first treatment phase; and administering hu5G11-hIgG1 and anlotinib hydrochloride to the patient in a second treatment phase.

[0255] The present disclosure provides a drug combination comprising hu5G11-hIgG1, doxorubicin, and anlotinib hydrochloride that can safely and effectively treat uterine malignancies. Patients with uterine malignancies experience beneficial effects in at least one of ORR, DCR, DOR, PFS, OS, tolerability, and side effects after receiving a treatment regimen comprising administering hu5G11-hIgG1, doxorubicin, and anlotinib hydrochloride to the patient in a first treatment phase; and administering hu5G11-hIgG1 and anlotinib hydrochloride to the patient in a second treatment phase.

[0256] The present disclosure provides a drug combination comprising hu5G11-hIgG1, gemcitabine, docetaxel, and anlotinib hydrochloride that can safely and effectively treat uterine malignancies. Patients with uterine malignancies experience beneficial effects in at least one of ORR, DCR, DOR, PFS, OS, tolerability, and side effects after receiving a treatment regimen comprising administering hu5G11-hIgG1, gemcitabine, docetaxel, and anlotinib hydrochloride to the patient in a first treatment phase; and administering hu5G11-hIgG1 and anlotinib hydrochloride to the patient in a second treatment phase.

[0257] In some embodiments, the treatment is a first-line treatment for a uterine malignancy. In some embodiments, the uterine malignancy is endometrial cancer and / or uterine sarcoma. In some embodiments, the first treatment phase comprises 6 to 8 treatment cycles. In some embodiments, one treatment cycle is every 3 weeks.

[0258] Definition and Description

[0259] Unless otherwise indicated, the following terms used in this disclosure have the following meanings. A particular term should not be construed as undefined or unclear unless specifically defined, but rather should be understood according to its ordinary meaning in the art. When a trade name appears in this disclosure, it is intended to refer to the corresponding commercial product or its active ingredient.

[0260] Herein, unless otherwise specified, the amount of anlotinib or its pharmaceutically acceptable salt refers to the amount of the active ingredient anlotinib free base.

[0261] Unless otherwise specified, the term "flat dose" refers to the dose administered to a patient regardless of the patient's weight or body surface area (BSA). A flat dose is therefore specified as an absolute amount of the agent, rather than as a mg / kg dose. For example, a 60 kg person and a 100 kg person would receive the same dose of an antibody (e.g., 1200 mg of an anti-PD-L1 antibody).

[0262] Herein, "complete response" (CR) refers to the disappearance of all target lesions.

[0263] In this article, "partial response" (PR) refers to a reduction of the total diameter of the target lesion by more than 30% compared with the baseline total diameter.

[0264] For the purposes of this article, "progressive disease" (PD) refers to an increase of 20% or greater in the total diameter of the target lesion compared to the smallest total diameter seen during the study (including the baseline total diameter, if that was the smallest value seen during the study). Furthermore, the absolute value of the total diameter must increase by at least 5 mm. The appearance of one or more new lesions is also considered progressive disease.

[0265] In this article, "stable disease" (SD) means that the lesion has shrunk but is not up to the standard of PR; or the lesion has enlarged but is not up to the standard of PD. The smallest diameter is used as a reference in the trial.

[0266] In this article, “best efficacy” refers to the best efficacy at all time points from the initial evaluation to the last evaluation.

[0267] The term "recurrent" cancer is a cancer that has regrown at the original site or at a distant site after responding to initial treatment (eg, surgery).

[0268] The term "metastatic" cancer refers to cancer that has spread from one part of the body (such as the uterus) to another part of the body.

[0269] As used herein, the term "pharmaceutical combination" refers to a combination of two or more active substances (administered as their respective active ingredients themselves, or as their respective pharmaceutically acceptable salts or esters, derivatives, prodrugs, or compositions) administered simultaneously or sequentially. The active substances may be administered to a patient simultaneously as a single formulation or sequentially in any order.

[0270] As used herein, the term "antibody" refers to an antigen-binding protein having at least one antigen-binding domain. The antibodies and fragments thereof disclosed herein may be whole antibodies or any fragments thereof. Therefore, the antibodies and fragments thereof disclosed herein include monoclonal antibodies or fragments thereof and antibody variants or fragments thereof. Examples of antibodies and antigen-binding fragments disclosed herein include monospecific antibodies, bispecific antibodies, multispecific antibodies, Fab fragments, Fab' fragments, F(ab)'2 fragments, Fv fragments, isolated CDR regions, single-chain Fv molecules (scFv), Fd fragments, and other antibody fragments known in the art. The PD-L1 antibodies or antigen-binding fragments thereof disclosed herein may be of the IgG1, IgG2, IgG3, or IgG4 isotype. The term "isotype" refers to the class of antibodies encoded by the heavy chain constant region gene. In some embodiments, the PD-L1 antibodies or antigen-binding fragments thereof disclosed herein are of the IgG1 or IgG4 isotype. The PD-L1 antibodies or antigen-binding fragments thereof disclosed herein may be derived from any species, including but not limited to mice, rats, rabbits, primates, llamas, and humans. The PD-L1 antibodies or antigen-binding fragments thereof disclosed herein may be murine antibodies, chimeric antibodies, humanized antibodies, or fully human antibodies. In one embodiment, the anti-PD-L1 antibody is a murine antibody. In another embodiment, the anti-PD-L1 antibody is a chimeric antibody. In another embodiment, the chimeric antibody is a mouse-human chimeric antibody. In another embodiment, the antibody is a humanized antibody. In another embodiment, the antibody is derived from a murine antibody and is humanized. A "humanized antibody" is an antibody that contains complementary determining regions (CDRs) derived from a non-human antibody and framework regions and constant regions derived from a human antibody. For example, the anti-PD-L1 antibodies described herein may comprise CDRs derived from one or more murine antibodies and human framework regions and constant regions. Thus, in one embodiment, the humanized antibodies described herein bind to the same epitope on PD-L1 as the murine antibody from which the CDRs of the antibody are derived. In some embodiments, the anti-PD-L1 antibody is a humanized antibody. Additional anti-PD-L1 antibodies or variants thereof comprising the heavy chain CDRs and light chain CDRs provided herein can be generated using any human framework sequence and are also included in the present disclosure. In one embodiment, framework sequences suitable for use in the present disclosure include those that are structurally similar to the framework sequences provided herein. Additional modifications may be made in the framework regions to improve the properties of the antibodies provided herein. Such additional framework modifications may include chemical modifications; point mutations to reduce immunogenicity or remove T cell epitopes; or reverting mutations to residues in the original germline sequence. In some embodiments, such modifications include those corresponding to the mutations exemplified herein, including back mutations to germline sequences.For example, in one embodiment, one or more amino acids in the human framework region of the VH and / or VL of the humanized antibodies described herein are backmutated to the corresponding amino acids in the parent murine antibody. Unless otherwise indicated, the "antibodies" of the present disclosure include whole antibodies and any antigen-binding fragments (or "antigen-binding portions") or single chains thereof. Conventional "whole antibodies" are glycoproteins comprising two heavy (H) chains and two light (L) chains, with the heavy and light chains linked by disulfide bonds. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of three domains, namely CH1, CH2 and CH3. Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region consists of one domain, CL. The VH and VL regions can also be divided into hypervariable regions, i.e., complementarity determining regions (CDRs), and framework regions (FRs) whose sequences are relatively conserved. Each VH and VL is composed of three CDRs and four FRs, respectively, from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant region of the antibody can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. At the same time, as will be appreciated by those skilled in the art, special "whole antibodies," such as nanobodies, have only heavy (H) chains and no light (L) chains.

[0271] An "antigen-binding fragment" or "antibody binding portion" of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen (e.g., PD-L1). It has been shown that the antigen-binding function of an antibody can be performed by fragments of the entire antibody. Examples encompassed by the term "antigen-binding portion / fragment" of an antibody include: (i) a Fab fragment: a monovalent fragment consisting of the VL, VH, CL, and CH1 domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments connected by a disulfide bridge at the hinge region; (iii) an Fd fragment consisting of the VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment consisting of a VH domain (see Ward et al., Nature. 341: 544-546 (1989)); (vi) an isolated complementarity-determining region (CDR); and (vii) a nanobody, a heavy chain variable region comprising a single variable domain and two constant domains. In addition, although the two domains VL and VH of the Fv fragment are encoded by different genes, VH and VL can be connected into a single protein chain by a recombinant method through a synthetic linker, wherein VL and VH pair to form a monovalent molecule (called single-chain Fv (scFv); see, for example, Bird et al., Science. 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. 85: 5879-5883 (1988)). These single-chain antibodies are also encompassed by the term antigen-binding portion / fragment. In addition, recombinant polypeptides, fusion proteins, and immunoconjugates comprising the antigen-binding portion / fragment are also encompassed by the term antigen-binding portion / fragment.

[0272] An "isolated antibody" refers to an antibody that is substantially free of other antibodies with different antigenic specificities (e.g., an isolated antibody that specifically binds PD-L1 is substantially free of antibodies that specifically bind antigens other than PD-L1). However, an isolated antibody that specifically binds PD-L1 may have cross-reactivity with other antigens, such as PD-L1 molecules from different species. Furthermore, an isolated antibody is substantially free of other cellular material and / or chemicals.

[0273] The terms "human PD-L1," "hPD-L1," and "huPD-L1," etc., are used interchangeably herein and refer to human PD-L1 and variants or isoforms of human PD-L1.

[0274] "Identity" refers to the similarity between two reference sequences, and percent identity refers to the percentage obtained by comparing sequences or specified regions of sequences using a sequence comparison algorithm well known to those skilled in the art.

[0275] The term "treat" generally refers to obtaining a desired pharmacological and / or physiological effect. The effect can be therapeutic in terms of partial or complete stabilization or cure of a disease and / or symptoms resulting from a disease. As used herein, "treat" encompasses any treatment of a disease in a patient, including: (a) suppressing the symptoms of a disease, i.e., arresting its progression; or (b) relieving the symptoms of a disease, i.e., causing regression of the disease or condition.

[0276] The term "first-line treatment" refers to the drug that can be selected first or standardly based on the patient's condition.

[0277] The term "prevention" means preventing a disease or one or more symptoms associated with a disease, and includes preventing a disease or disease state from occurring in a mammal, particularly when such mammal is susceptible to the disease state but has not yet been diagnosed with the disease state. As used herein, the term "systemic treatment" refers to treatment in which a drug substance is delivered through the bloodstream to reach and affect cells throughout the body.

[0278] As used herein, the term "systemic therapy" refers to systemic chemotherapy, systemic or local radiotherapy. The term "first-line systemic therapy" refers to the systemic therapy that can be selected first or standardly based on the patient's condition.

[0279] The term "adjuvant therapy" refers to any treatment given after primary treatment (ie, surgery) to increase the chance of long-term survival, and "neoadjuvant therapy" refers to treatment given before primary treatment (ie, surgery).

[0280] The term "treatment failure" is defined as disease progression during treatment or after the last treatment; or intolerable toxic side effects during treatment.

[0281] The term "effective amount" means an amount of a compound of the present disclosure that (i) treats a specific disease, condition, or disorder, (ii) alleviates, ameliorates, or eliminates one or more symptoms of a specific disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of a specific disease, condition, or disorder described herein. The amount of active substance (e.g., an antibody or compound of the present disclosure) that constitutes a "therapeutically effective amount" may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the therapeutic agent or combination of therapeutic agents to elicit a desired response in the individual. An effective amount can also be routinely determined by one skilled in the art based on their own knowledge and the present disclosure.

[0282] The term "administer" means that a therapeutic agent is physically introduced into a subject using any of a variety of methods and delivery systems known to those skilled in the art. The route of administration of the anti-PD-L1 antibody or antigen-binding fragment thereof includes a parenteral route of administration (including but not limited to intravenous, intramuscular, subcutaneous, intraperitoneal, spinal or other parenteral routes of administration), such as by injection or infusion. In some embodiments, the phrases "parenteral administration" or "parenteral administration" as used herein are used interchangeably and generally refer to modes of administration other than enteral and topical administration by injection, and include but are not limited to intravenous, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion, and in vivo electroporation. In certain embodiments, the anti-PD-L1 antibody or antigen-binding fragment thereof is administered via a non-parenteral route; in certain embodiments, oral administration; other non-parenteral routes include topical, epidermal, or mucosal administration, for example, intranasal, intravaginal, intrarectal, sublingual, or topical administration. Administration can also be performed, for example, once, multiple times, and / or over one or more extended periods of time.

[0283] The term "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms that are suitable for use in contact with the tissues of humans and animals without excessive toxicity, irritation, allergic response, or other problems or complications.

[0284] The term "pharmaceutically acceptable salt" includes salts formed between a free base and an acid, or between an acid and a free base, including, for example, hydrochloride, hydrobromide, nitrate, sulfate, phosphate, formate, acetate, trifluoroacetate, fumarate, oxalate, maleate, citrate, succinate, methanesulfonate, benzenesulfonate, or p-toluenesulfonate; in some embodiments, hydrochloride, hydrobromide, sulfate, formate, acetate, trifluoroacetate, fumarate, maleate, methanesulfonate, p-toluenesulfonate, sodium salt, potassium salt, ammonium salt, amino acid salt, etc. In the present disclosure, when forming a pharmaceutically acceptable salt, the molar ratio of the acid to the free base is 1:0.2-1:5; in some embodiments, it is 1:0.5, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, or 1:8.

[0285] As used herein, a "patient" or "subject" is a mammal, such as a rodent, feline, canine, and primate. In some embodiments, the patient is a human. In some embodiments, the subject is a human. A "subject" includes any human or non-human animal. "Non-human animals" include, but are not limited to, vertebrates such as non-human primates, sheep, dogs, and rodents such as mice, rats, and guinea pigs. The terms "patient," "subject," and "subject" are used interchangeably in certain contexts herein.

[0286] The term "chemotherapy regimen" includes one or more chemotherapy drugs.

[0287] The term "single dose" refers to the smallest packaging unit containing a specific amount of a drug. For example, if a box of medicine contains seven tablets, one tablet is a single dose; or a bottle of injection is a single dose. A "unit dose" refers to the amount of active ingredient contained in the smallest packaging unit containing a specific amount of a drug. For example, the amount of antibody contained in a bottle of antibody injection is a unit dose. The term "multiple doses" refers to a combination of multiple single doses.

[0288] The term "pharmaceutical composition" refers to a mixture of one or more active ingredients of the present disclosure or pharmaceutical combinations thereof with pharmaceutically acceptable excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound of the present disclosure or pharmaceutical combination thereof to a patient. As used herein, the terms "pharmaceutical composition" and "formulation" have the same meaning and are used interchangeably.

[0289] Herein, unless otherwise stated, the terms "comprise, comprise, and comprising" or equivalents are open-ended expressions, meaning that in addition to the listed elements, components, and steps, other unspecified elements, components, and steps may also be included.

[0290] As used herein, the indefinite article "a" or "an" should be understood to mean "one or more" of any listed or enumerated components. In the claims and / or specification of the present disclosure, referents such as "a, an," "said," or "the" are intended to support both the singular and / or the plural, unless the context indicates otherwise.

[0291] The terms "about," "approximately," or "substantially encompass" refer to a value or composition that is within an acceptable error range for a particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, "about," "approximately," or "substantially encompass" can mean within 1 or more than 1 standard deviation, as practiced in the art. Alternatively, "about" or "substantially encompass" can mean a range that differs by up to 10% or 20% (i.e., ±10% or ±20%) from the parameter or value modified by it. For example, about 3 mg can include any number between 2.7 mg and 3.3 mg (for 10%) or between 2.4 mg and 3.6 mg (for 20%). In addition, particularly with respect to biological systems or processes, the term can mean up to an order of magnitude or up to 5 times the value. When a particular value or composition is provided in the present disclosure and claims, unless otherwise indicated, the meaning of "about" or "substantially encompass" should be assumed to be within an acceptable error range for that particular value or composition.

[0292] As described herein, any concentration range, percentage range, ratio range, or integer range should be understood to include the value of any integer within the recited range, and, where appropriate, fractions thereof (such as tenths and hundredths of integers), unless otherwise indicated.

[0293] As used herein, "combination" or "combined use" means that two or more active substances may be administered to a subject together in a mixture, simultaneously as a single formulation, or sequentially in any order as a single formulation.

[0294] The "clinical benefit" in this disclosure includes, but is not limited to: prolonged progression-free survival (PFS) of clinical patients, prolonged overall survival (OS), improved objective response rate (ORR), improved disease control rate (DCR), prolonged objective response time (TTR), and reduced number and / or severity of adverse reactions.

[0295] The system used to stage endometrial cancer is the FIGO (International Federation of Gynecology and Obstetrics) system. Endometrial cancer is classified based on three factors: the extent of the tumor, whether the cancer has spread to lymph nodes, and whether the cancer has spread to distant sites. Information about the tumor, lymph nodes, and any spread of the cancer is then combined to determine the stage of the disease, a procedure called stage grouping. Roman numerals from I to IV describe these stages. Some stages are divided into substages (represented by letters and numbers).

[0296] For the purpose of description and disclosure, all patents, patent applications and other publications are expressly incorporated herein by reference. These publications are provided only because their disclosure predates the filing date of the present disclosure. All statements about the dates of these documents or the description of the contents of these documents are based on the information available to the applicant and do not constitute any admission as to the correctness of the dates of these documents or the contents of these documents. Furthermore, any citation of these publications in this document does not constitute an admission that such publications become part of the common general knowledge in the art in any country. DETAILED DESCRIPTION

[0297] For the sake of clarity, the present disclosure is further illustrated by examples, but the examples do not limit the scope of the present disclosure. All reagents used in the present disclosure are commercially available and can be used without further purification. The anti-PD-L1 antibody hu5G11-hIgG1 in the embodiment (heavy chain amino acid sequence is shown in SEQ ID NO: 17, and light chain amino acid sequence is shown in SEQ ID NO: 18) can be prepared according to the method described in WO2016022630, and can also be prepared with reference to the amino acid sequence of benmelstobart disclosed in WHO Drug Information, Vol. 36, No. 4, 2022.

[0298] Example 1 Clinical Trial

[0299] The treatment process is divided into the first treatment phase and the maintenance treatment phase (i.e., the second treatment phase). Each 3-week (21-day) treatment cycle is a treatment cycle. Patients first receive 6 to 8 treatment cycles in the first treatment phase, and then enter the maintenance treatment phase, which continues until they lose clinical benefit, toxicity is unacceptable, efficacy evaluation is disease progression, or the investigator deems it inappropriate to continue the drug.

[0300] 1.1 Main inclusion criteria:

[0301] 1) The subjects voluntarily participated in this study, signed the informed consent form, and had good compliance.

[0302] 2) Age: ≥18 years old (at the time of signing the informed consent); ECOG PS score: 0-1; expected survival time more than 3 months; body mass index (BMI) >18.5 and weight >40 kg.

[0303] 3) Have not received first-line systemic anticancer treatment and are not suitable for other treatments except systemic treatment;

[0304] Cohorts 1 and 2: Patients with histopathologically confirmed stage III / IV or recurrent epithelial endometrial cancer (including endometrioid carcinoma, non-endometrioid carcinoma, and carcinosarcoma), and who also meet any of the following categories:

[0305] i) Newly diagnosed subjects: those with radiographically visible residual lesions after non-radical surgery or those who have not undergone surgery (those who have not undergone surgery are not suitable for surgery and radical radiotherapy);

[0306] ii) Subjects with first relapse: The time of relapse is greater than 12 months from the end of initial treatment (complete remission after surgery or surgery plus adjuvant therapy); or the subject receives systemic platinum-based adjuvant and / or neoadjuvant chemotherapy (chemotherapy alone, concurrent chemoradiotherapy, or as sequential therapy, complete remission after treatment), and the disease relapses more than 6 months after the last chemotherapy;

[0307] Cohort 3: Patients with histopathologically confirmed stage I-IV uterine sarcoma and who also meet any of the following categories:

[0308] i) Newly diagnosed / first recurrence of high-grade endometrial stromal sarcoma (ESS), undifferentiated uterine sarcoma (UUS), uterine leiomyosarcoma (uLMS), and adenosarcoma with sarcoma overgrowth (SO). The definitions of new diagnosis and first recurrence are the same as above;

[0309] ii) Low-grade ESS and adenosarcoma without SO or ER who have failed previous anti-estrogen therapy + / PR + Other uterine sarcomas;

[0310] Note: Newly diagnosed subjects who did not receive radiotherapy after surgery can start treatment with the trial drug within 8 weeks after surgery; those who received radiotherapy after surgery can start treatment with the trial drug within 8 weeks after surgery; adjuvant treatment includes external beam radiotherapy (EBRT), vaginal afterloading radiotherapy, and radiotherapy + chemotherapy; sarcoma overgrowth is defined as a pathology report indicating that high-grade sarcomatoid components account for more than 25% of the total tumor volume.

[0311] 4) According to RECIST 1.1 criteria, there is at least one measurable lesion. If the measurable lesion is located in the area previously treated with radiotherapy, it should be clearly considered to be in a progressive state.

[0312] 5) Tumor tissue samples can be provided for testing of MSI / MMR status or traceable test reports.

[0313] 6) Major organ functions are good and meet the following criteria:

[0314] i) Routine blood test criteria (no blood transfusion or use of hematopoietic stimulating factor drugs within 7 days before screening): hemoglobin (HGB) ≥ 90 g / L; absolute neutrophil count (NEUT) ≥ 1.5 × 10 9 / L; platelet count (PLT) ≥90×10 9 / L;

[0315] ii) Biochemical examinations must meet the following criteria: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; if liver metastasis is present, ALT and AST ≤ 5 × ULN; serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (Ccr) ≥ 60 mL / min; serum albumin (ALB) > 30 g / L;

[0316] iii) Urinalysis standard: Urinalysis indicates urine protein <++; if urine protein ≥++, it is necessary to confirm that the 24-hour urine protein is ≤1.0g;

[0317] iv) Coagulation function or thyroid function tests must meet the following criteria: prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5 × ULN (not receiving anticoagulant therapy); thyroid stimulating hormone (TSH) ≤ ULN. If abnormal, triiodothyronine (T3) and thyroxine (T4) levels should be checked. Patients with normal T3 and T4 levels are eligible for inclusion.

[0318] v) Echocardiography assessment: left ventricular ejection fraction (LVEF) ≥ 50%;

[0319] vi) 12-lead electrocardiogram assessment: QTc < 470 ms.

[0320] 7) Female subjects must agree to use contraceptive measures (such as intrauterine devices or condoms) during the study and within 6 months after the end of the study; the serum pregnancy test must be negative within 7 days before study enrollment, and the subjects must be non-breastfeeding.

[0321] 1.2 Investigational Drugs

[0322] Anti-PD-L1 antibody hu5G11-hIgG1 injection (600 mg / 20 mL): Administer 1200 mg of hu5G11-hIgG1 via intravenous infusion over 60 ± 10 minutes. Administer hu5G11-hIgG1 injection on day 1 (d1) of each treatment cycle and once every 3 weeks (21 days) (d1 / Q3W). Each 3-week (21-day) treatment cycle constitutes one treatment cycle.

[0323] Anlotinib Hydrochloride Capsules (active ingredient is anlotinib dihydrochloride) (Specifications: 12mg / capsule, 10mg / capsule, 8mg / capsule, 6mg / capsule): Take one capsule (10mg or 8mg) once daily (orally before breakfast). Take orally for 2 consecutive weeks and rest for 1 week, that is, 21 days as a treatment cycle, and administer the drug on days 8-21 of each treatment cycle. Unless there are special circumstances, it is recommended to take the drug at a fixed time every day. If a dose is missed during the medication period, no supplemental dose is required if the next dose is confirmed to be less than 12 hours away (i.e., 10mg / qd or 8mg / qd, d8-21 / Q3W). Researchers can adjust the dose of anlotinib hydrochloride capsules based on the disease condition and safety, for example: 12mg / qd, 10mg / qd, 8mg / qd, 6mg / qd.

[0324] Paclitaxel injection: 175 mg / m 2 The dose (calculated as paclitaxel) is administered by intravenous infusion over a period of more than 3 hours on day 1 (d1) of each treatment cycle and once every 3 weeks (21 days) (d1 / Q3W). One treatment cycle consists of 3 weeks (21 days).

[0325] Carboplatin injection: Administer by intravenous infusion at a dose of AUC = 5 mg / mL / min (calculated as carboplatin) on the first day (d1) of each treatment cycle and once every 3 weeks (21 days) (d1 / Q3W).

[0326] The dosage of carboplatin injection needs to be calculated based on the area under the plasma concentration-time curve (AUC) and endogenous creatinine clearance. The AUC (mg / mL / min) value is 5.

[0327] Calvert formula for carboplatin dosing based on AUC:

[0328] Carboplatin dose (mg) = assumed AUC (mg / mL / min) × [creatinine clearance (mL / min) + 25]

[0329] Endogenous creatinine clearance was calculated using the Cockcroft-Gault formula:

[0330] Doxorubicin hydrochloride for injection: 60 mg / m 2 The dose (calculated as doxorubicin hydrochloride) is administered intravenously, with an intravenous push over 5-10 minutes and an intravenous infusion over 90-120 minutes, on day 1 (d1) of each treatment cycle and once every 3 weeks (21 days) (d1 / Q3W). Every 3 weeks (21 days) constitutes one treatment cycle.

[0331] Gemcitabine hydrochloride for injection: 900 mg / m 2The dose (calculated as gemcitabine) is administered by intravenous infusion over 30 minutes on Day 1 (d1) and Day 8 (d8) of each treatment cycle, and on Day 1 and Day 8 every 3 weeks (d1, d8 / Q3W). One treatment cycle consists of 3 weeks (21 days).

[0332] Docetaxel injection: 75 mg / m 2 The dose (calculated as docetaxel) was administered by intravenous infusion over 60 minutes on day 8 (d8) of each treatment cycle and once every 3 weeks (21 days) (d1 / Q3W). One treatment cycle consisted of 3 weeks (21 days).

[0333] The first day of each treatment cycle is d1, the eighth day of each treatment cycle is d8, and the twenty-first day of each treatment cycle is d21.

[0334] 1.3 Dosage Regimen The treatment process is divided into the first treatment phase and the maintenance treatment phase (i.e., the second treatment phase). The first treatment phase (6-8 treatment cycles) and the maintenance treatment phase (continue from the end of the first treatment phase until the patient loses clinical benefit, toxicity is unacceptable, the efficacy evaluation is PD, or the researcher deems it inappropriate to continue the medication) are as follows: The researcher may adjust the dose of Anlotinib Hydrochloride Capsules based on the disease status and safety, for example: 12 mg / qd, 10 mg / qd, 8 mg / qd, 6 mg / qd.

[0335] Queue 1:

[0336] First treatment phase: hu5G11-hIgG1 injection 1200 mg, d1 / Q3W; carboplatin injection AUC = 5 mg / ml.min, d1 / Q3W; and paclitaxel injection 175 mg / m 2 , d1 / Q3W;

[0337] Second treatment phase: hu5G11-hIgG1 injection 1200 mg, d1 / Q3W.

[0338] Queue 2:

[0339] First treatment phase: hu5G11-hIgG1 injection 1200 mg, d1 / q3W; anlotinib hydrochloride capsule 8 mg / qd, d8-21 / q3W; carboplatin injection AUC = 5 mg / ml.min, d1 / q3W; and paclitaxel injection 175 mg / m 2 , d1 / Q3W;

[0340] Second treatment phase: hu5G11-hIgG1 injection 1200 mg, d1 / Q3W; and anlotinib hydrochloride capsules 10 mg / qd, d8-21 / Q3W.

[0341] Queue 3:

[0342] The first treatment phase: hu5G11-hIgG1 injection 1200 mg, d1 / Q3W; anlotinib hydrochloride capsule 8 mg / qd, d8-21 / Q3W; and chemotherapy (doxorubicin hydrochloride injection 60 mg / m 2 , d1 / Q3W; or gemcitabine hydrochloride for injection 900mg / m 2 d1, d8 / Q3W+docetaxel injection 75mg / m 2 , d1 / Q3W)

[0343] Second treatment phase: hu5G11-hIgG1 injection 1200 mg, d1 / Q3W; and anlotinib hydrochloride capsules 10 mg / qd, d8-21 / Q3W.

[0344] 1.4 Evaluation Criteria

[0345] Efficacy evaluation criteria: RECIST 1.1 and iRECIST were used to assess disease status. RECIST 1.1 was the primary evaluation standard, while iRECIST was also used to confirm efficacy.

[0346] Safety evaluation criteria: The NCI-CTC AE 5.0 standard was used to judge the severity of adverse events.

[0347] 1.5 Study Endpoints

[0348] Primary endpoint: Investigator-assessed objective response rate (ORR).

[0349] Secondary endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR); the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and abnormal laboratory test indicators.

[0350] 1.6 Test results

[0351] A total of 28 patients have been recruited so far, with 10 patients in cohort one and 18 patients in cohort two.

[0352] Preliminary studies have shown that a drug combination containing hu5G11-hIgG1, carboplatin, and paclitaxel can safely and effectively treat endometrial cancer. As of the data statistics date, in this study, 5 subjects in cohort 1 completed at least 2 cycles of treatment. Among them, the best assessed efficacy of 3 subjects (3 / 5) was PR (partial response), and the best assessed efficacy of 2 subjects (2 / 5) was SD (stable disease). The objective response rate (ORR) reached 60% and the disease control rate (DCR) reached 100%. It is worth mentioning that after subject 101 completed 2 cycles of treatment, the target lesion completely disappeared. The patient continued to receive treatment in the group, and his best assessed efficacy is expected to achieve CR. The specific results are shown in Table 2.

[0353] Preliminary studies have shown that a drug combination containing hu5G11-hIgG1, carboplatin, paclitaxel, and anlotinib hydrochloride can safely and effectively treat endometrial cancer. As of the data collection date, 12 subjects in Cohort 2 of this study completed at least two treatment cycles. Among them, one subject (1 / 12) achieved a best-assessed response of CR (complete response), eight subjects (8 / 12) achieved a best-assessed response of PR (partial response), and three subjects (3 / 12) achieved a best-assessed response of SD (stable disease). The objective response rate (ORR) reached 75% and the disease control rate (DCR) reached 100%. It is worth noting that after completing two treatment cycles, subjects 009 and 010 achieved complete disappearance of target lesions. The patients continue to receive treatment in the group, and their best-assessed response is expected to achieve CR. The specific results are shown in Table 3.

[0354] Table 1. Exemplary Subject Characteristics

[0355] Table 2. Specific results

[0356] Table 3. Specific results

[0357] Note: “ / ” indicates that the treatment cycle has not yet been reached.

Claims

1. A pharmaceutical combination comprising an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug for the treatment of uterine malignancies, wherein: The anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a heavy chain CDR1 region as shown in SEQ ID NO: 1, a heavy chain CDR2 region as shown in SEQ ID NO: 2, a heavy chain CDR3 region as shown in SEQ ID NO: 3, a light chain CDR1 region as shown in SEQ ID NO: 7, a light chain CDR2 region as shown in SEQ ID NO: 8, and a light chain CDR3 region as shown in SEQ ID NO:

9.

2. The use according to claim 1, wherein The anti-PD-L1 antibody or antigen-binding fragment thereof comprises: a) a heavy chain variable region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 13, and a light chain variable region that is at least 80% homologous to the amino acid sequence of SEQ ID NO: 15; or b) a heavy chain that is at least 80% homologous to the amino acid sequence shown in SEQ ID NO: 17, and a light chain that is at least 80% homologous to the amino acid sequence shown in SEQ ID NO:

18.

3. The use according to claim 1 or 2, wherein The drug combination further includes anlotinib or a pharmaceutically acceptable salt thereof.

4. The use according to any one of claims 1 to 3, wherein The drug combination includes a first drug combination and, optionally, a second drug combination; the first drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and a chemotherapy drug.

5. The use according to claim 4, wherein The second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof.

6. The use according to claim 4, wherein The first drug combination further includes anlotinib or a pharmaceutically acceptable salt thereof.

7. The use according to claim 6, wherein The second drug combination includes an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof.

8. The use according to any one of claims 4 to 7, wherein The first drug combination is administered to a patient in need thereof during a first treatment phase, and optionally, the second drug combination is administered to a patient in need thereof during a second treatment phase; the first treatment phase comprises 1 to 14 treatment cycles, 2 to 12 treatment cycles, preferably 4 to 10 treatment cycles, and most preferably 6 to 8 treatment cycles; Optionally, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably one treatment cycle is every 3 weeks.

9. The use according to any one of claims 1 to 8, wherein The chemotherapy drug is selected from one or more of platinum anti-tumor drugs, taxane anti-tumor drugs, anthracycline anti-tumor drugs, and antimetabolite anti-tumor drugs; Optionally, the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenanthreneplatin, and satraplatin; Optionally, the taxane anti-tumor drug is selected from one or more of paclitaxel, liposome paclitaxel, albumin-bound paclitaxel, and docetaxel; Optionally, the anthracycline anti-tumor drug is selected from one or more of doxorubicin, liposome doxorubicin, epirubicin, pirarubicin, amrubicin, aclarubicin, idarubicin, daunorubicin, mitoxantrone, idarubicin, valrubicin, daunorubicin, pixantrone, and liposomal doxorubicin; Optionally, the antimetabolite anti-tumor drug is selected from one or more of carmofur, 5-fluorouracil, tegafur, capecitabine, S-1, fluorouracil, doxifluridine, trifluridine, cytarabine, gemcitabine, azacitidine, ancitabine, mercaptopurine, fludarabine, methotrexate, and pemetrexed; Optionally, the chemotherapy drug is selected from carboplatin and paclitaxel, or the chemotherapy drug is selected from doxorubicin, or the chemotherapy drug is selected from docetaxel and gemcitabine.

10. The use according to claim 9, wherein In the first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin are administered to patients in need. In the second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof is administered to patients in need. The first treatment phase comprises 6 to 8 treatment cycles, with each cycle consisting of 3 weeks. The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle; The dosing regimen of the second treatment phase includes administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle.

11. The use according to claim 9, wherein In the first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, carboplatin, and anlotinib or a pharmaceutically acceptable salt thereof are administered to patients in need thereof. In the second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof are administered to patients in need thereof. The first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks constituting one treatment cycle. The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, paclitaxel, and carboplatin on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle; The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

12. The use according to claim 9, wherein In the first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, doxorubicin and anlotinib or a pharmaceutically acceptable salt thereof are administered to patients in need thereof. In the second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof are administered to patients in need thereof. The first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks being one treatment cycle. The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof and doxorubicin on day 1 of each treatment cycle; administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle; The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

13. The use according to claim 9, wherein In the first treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof, gemcitabine, docetaxel, and anlotinib or a pharmaceutically acceptable salt thereof are administered to patients in need thereof. In the second treatment phase, an anti-PD-L1 antibody or an antigen-binding fragment thereof and anlotinib or a pharmaceutically acceptable salt thereof are administered to patients in need thereof. The first treatment phase comprises 6 to 8 treatment cycles, with each 3 weeks constituting one treatment cycle. The dosing regimen of the first treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof, gemcitabine, and docetaxel on day 1 of each treatment cycle; administering gemcitabine on day 8 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily from day 8 to day 21 of each treatment cycle. The dosing regimen of the second treatment phase includes: administering an anti-PD-L1 antibody or an antigen-binding fragment thereof on day 1 of each treatment cycle; and administering anlotinib or a pharmaceutically acceptable salt thereof daily on days 8-21 of each treatment cycle.

14. The use according to any one of claims 1 to 13, wherein The uterine malignancy is endometrial cancer or uterine sarcoma.

15. The use according to any one of claims 1 to 14, wherein The treatment is first-line treatment for endometrial cancer or uterine sarcoma.