54 results about "Pembrolizumab" patented technology

Provided is a stable pharmaceutical composition comprising an anti-PD-1 antibody. More particularly, the present invention relates to a pharmaceutical composition of pembrolizumab. The stability of the composition is ensured while the viscosity of a formulation is reduced, effectively solving the problems of high-concentration antibody formulations in drug manufacturing, storage and transportation, and drug delivery.

The present invention relates to compositions and methods for treating cancer in a patient comprising administering to the patient subcutaneously every six weeks a specific amount of a PD-1 antagonist, e.g., an anti-PD-1 antibody (e.g., pemmumab) or an antigen-binding fragment thereof, with or without a hyaluronidase. In particular embodiments, the amount of the anti-PD-1 antibody or antigen-binding fragment thereof is from about 600 mg to about 1000 mg. In particular embodiments, the administration is performed once every about three weeks, and the amount of the anti-PD-1 antibody or antigen-binding fragment thereof is from about 300 mg to about 500 mg. In certain embodiments, the PD-1 antagonist is pembromab or an antigen binding fragment thereof. Also provided are compositions and kits formulated for subcutaneous administration comprising specific doses of an anti-PD-1 antibody or antigen-binding fragment thereof, and uses thereof for the treatment of cancer.

Disclosed herein are compositions and methods for treating cancer, specifically extensive-stage small-cell lung cancer (ES-SCLC), through the administration of a combination therapy. In some embodiments, the method comprises administering plinabulin, one or more immune checkpoint inhibitors, including but not limited to pembrolizumab, and a regimen of etoposide with a platinum-based agent (EP). The disclosed methods enhance tumor reduction, prolong progression-free survival, and improve overall treatment efficacy compared to traditional therapies.

The invention relates to compositions and methods for treating cancer in a patient comprising subcutaneously administering a PD-1 antagonist, e.g., an anti-PD-1 antibody (e.g. pembrolizumab), or antigen binding fragment thereof, with or without hyaluronidase every six weeks, in specific amounts to the patient. In specific embodiments, the amount of anti-PD-1 antibody, or antigen binding fragment thereof, is about 600 mg to about 1000 mg. In specific embodiments, the administration occurs about every three weeks, and the amount of anti-PD-1 antibody, or antigen binding fragment thereof, is about 300 mg to about 500 mg. In certain embodiments, the PD-1 antagonist is pembrolizumab, or an antigen binding fragment thereof. Also provided are compositions and kits formulated for subcutaneous administration comprising a particular dosage of an anti-PD-1 antibody, or antigen-binding fragment thereof, and uses thereof for treating cancer.

A clinical combination therapy comprising one or more pharmaceutical compositions for treating various cancers. The one or more pharmaceutical compositions include at least a first composition of an immune checkpoint inhibitor and a second composition that interacts with an extracellular matrix component of the tumor microenvironment. The first composition may, for example, include pembrolizumab, and the second composition may include an LAIR-2Fc fusion protein, such as NC410. The compositions follow a dosing and timing regimen.

The present invention aims to solve the problem of providing a novel combination therapy with excellent antitumor effects. The present invention provides an antitumor agent (excluding pembrolizumab as an active ingredient) which includes as an active ingredient, fobamintib or a pharmaceutically acceptable salt thereof, to be administered in combination with an immune checkpoint inhibitor (excluding a CD155 / TIGIT pathway antagonist) and at least one or more other antitumor agents to a cancer patient.

A system for treating cancer is disclosed. According to an embodiment of the present invention, the system comprises: an electric field applying device for applying an electric field for tumor treatment; the delivery system is used for delivering a drug, and the drug comprises at least one of an immune checkpoint inhibitor and a chemical drug; the immune checkpoint inhibitor is selected from one of a duvaleriumab, a palbolizumab, an atelizumab, a Nasuliumab and a tereprenil monoclonal antibody; the chemical drug is selected from at least one of gemcitabine, cis-platinum, GEMOX and lenvatinib. According to the system, proliferation of the biliary tract cancer cells can be inhibited, migration of the biliary tract cancer cells can be inhibited, mitosis of the biliary tract cancer cells can be interfered, and immunogenic death of the biliary tract cancer cells can be promoted.

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g. anti-PD1 antibody) could efficiently repress tumor growth in human cancer. The present invention also relates to multispecific antibodies comprising at least one binding site that specifically binds to an immune checkpoint molecule (e.g. PD-1), and at least one binding site that specifically binds to NRP-1. The present invention also relates to a population of cells engineered to express a chimeric antigen receptor (CAR) and wherein the expression of NRP-1 in said cells is repressed.

The present invention relates to the application of Clostridium ghonii spores and pembrolizumab in the treatment of cancer. The present invention is the first to discover that the combination of Clostridium ghonii spores and pembrolizumab can significantly improve the therapeutic effect of colon cancer, while reducing the dose of pembrolizumab, with high efficiency and low toxicity. The tumor lysis of Clostridium ghonii can affect TME immunogenicity in various ways, transform TME from an immunosuppressive state to an immunoactive state, and at the same time, regulate immunosuppressive TME and break immune resistance. Under optimal combination conditions, the combination of Clostridium ghonii spores and pembrolizumab completely eliminated about 20% of mouse tumor tissues, expanding the scope of benefit of tumor patients treated with PD-1 antibody, and even showing remarkable therapeutic effects in patients who failed PD-1 antibody treatment.

Biomarkers useful for identifying a variety of cancers that are responsive to treatment with a combination therapy comprising pembrolizumab, a pembrolizumab variant or an antigen-binding fragment thereof and talimogene laherparepvec are provided. Methods of treating cancers that are resistant to monotherapy with pembrolizumab, a pembrolizumab variant or an antigen-binding fragment thereof are provided. Methods of treating a cancer in a subject having a tumor with a low CD8+ density, a low or negative interferon gamma signature, and / or a low or negative PD-L1 status are also provided.

The present invention relates to methods of treating head and neck squamous cell carcinoma (HNSCC), such as metastatic or advanced HNSCC, in a subject in need thereof, comprising administering a therapeutically effective amount of an antibody to the subject, wherein the antibody specifically binds epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met) in addition to a PD-(L)1 axis inhibitor (pembrolizumab) and a platinum-based chemotherapy agent (carboplatin). In particular, the EGFR / c-Met antibody is amivantamab.

Provided herein are methods of treating KRAS G12C-positive NSCLC by administering a combination of a KRAS G12C inhibitor and pembrolizumab with a prophylactic dose of a steroid.

The invention relates to compositions and methods for treating cancer in a patient comprising subcutaneously administering a PD-1 antagonist, e.g., an anti-PD-1 antibody (e.g. pembrolizumab), or antigen binding fragment thereof, with or without hyaluronidase every six weeks, in specific amounts to the patient. In specific embodiments, the amount of anti-PD-1 antibody, or antigen binding fragment thereof, is about 1000 mg to about 1800 mg. In specific embodiments, the administration occurs about every three weeks, and the amount of anti-PD-1 antibody, or antigen binding fragment thereof, is about 500 mg to about 900 mg. In certain embodiments, the PD-1 antagonist is pembrolizumab, or an antigen binding fragment thereof. Also provided are compositions and kits formulated for subcutaneous administration comprising a particular dosage of an anti-PD-1 antibody, or antigen-binding fragment thereof, and uses thereof for treating cancer.

To provide peptide vaccines and pembrolizumab for treating breast cancer.SOLUTION: The disclosure features, inter alia, combination therapies comprising pembrolizumab and one or more immunogenic XBP1-, CD138-, and CS1-derived peptides. The therapies herein can be used, e.g., for inducing an immune response in a subject having a cancer, and treating a cancer such as breast cancer, e.g., triple negative breast cancer. In embodiments, the immunogenic peptides bind to MHC class 1 molecules such as HLA-A molecules. Peptides from X-Box Protein 1 (XBP1)-, CD 138-, and CD2 Subset 1 (CS1) are immunogenic and are useful, e.g., to induce an immune response against various cancer cells.SELECTED DRAWING: None

Disclosed herein is a method for predicting whether a subject with cancer will exhibit a beneficial response to arginine deficiency therapy. The method includes the step of determining the plasma concentration of arginine in the subject, followed by administering arginine deficiency therapy to the subject alone or in combination with an anticancer agent, based on the determined plasma concentration of arginine. According to some embodiments of this disclosure, the anticancer agent is selected from the group consisting of FOLFOX, docetaxel, cisplatin, pemetrexed, pembrolizumab, and combinations thereof.

The present invention relates to methods for treating cancer in a patient comprising administering a PD-1 antagonist, e.g., an anti-PD-1 antibody or antigen binding fragment thereof (e.g. pembrolizumab), in specific amounts to the patient about every six weeks. In some embodiments, the amount of anti-PD-1 antibody or antigen binding fragment thereof is about 400 mg. In certain embodiments, the PD-1 antagonist is pembrolizumab, or an antigen binding fragment thereof. Also provided are compositions and kits comprising a dosage of an anti-PD-1 antibody, or antigen-binding fragment thereof, and uses thereof for treating cancer.

This application provides a composition and method for treating cancer, including advanced metastatic cancer, using an activatable anti-CTLA4 antibody in combination with pembrolizumab.

The present application provides compositions and methods for the treatment of cancer, including advanced metastatic cancer, using an anti-CTLA4 antibody in combination with pemmumab.

The present invention is directed to methods of maintenance treatment for platinum sensitive ovarian cancer, wherein the methods comprise administering an anti-PVRIG antibody, optionally in combination with anti-TIGIT antibodies and / or anti-PD-1 antibodies, including the use of stable liquid pharmaceutical formulations thereof, in particular of the anti-PVRIG antibodies. Also provided are combination therapies for the treatment of cancer refractory or resistant to at least two or more prior therapeutic treatments, wherein the treatment comprises anti-PVRIG antibodies, anti-TIGIT antibodies, and pembrolizumab, including the use of stable liquid pharmaceutical formulations thereof, in particular of the anti-PVRIG antibodies.

The present disclosure provides a high-concentration composition of a PD-1 antibody and a method for preparing the same, which comprises pembrolizumab, wherein a portion of the pembrolizumab comprises a glucuronidation modification at the lysine at position 27 of the light chain of the amino acid sequence set forth in SEQ ID NO: 2, and wherein the content of the light chain of the pembrolizumab comprising the glucuronidation modification is less than or equal to 3% based on the percentage of the total content of the light chain of the pembrolizumab in the composition. The present disclosure also provides a pharmaceutical preparation comprising the above-mentioned composition. The present disclosure additionally provides a method for detecting the above-mentioned pembrolizumab comprising the glucuronidation modification and the use thereof in quality inspection or quality control of a product containing pembrolizumab.

The invention provides an application of a combination of plinabulin, palbolizumab and docetaxel in preparation of a medicine or a medicine box. Specifically, the drug or kit is administered to a subject having the following types: a metastatic non-small cell lung cancer patient who fails in first-line immune checkpoint inhibitor single drug therapy; and / or a metastatic non-small cell lung cancer patient who fails to be treated by a first-line immune checkpoint inhibitor combined with a chemotherapeutic drug.

The present invention provides methods for producing crystalline anti-PD-1 monoclonal antibodies (mAbs), wherein the mAbs are pembrolizumab or pembrolizumab variants, comprising (1) mixing a solution comprising (a) a mAb, (b) polyethylene glycol (PEG), and (c) an additive selected from the group consisting of caffeine, theophylline, 2'-deoxyguanosine-5'-monophosphate, a biologically active gibberellin, and a pharmaceutically acceptable salt of the biologically active gibberellin to form a crystallization solution; (2) incubating the crystallization solution for a time sufficient for crystal formation; and (3) optionally harvesting the crystalline anti-PD-1 mAb from the solution. In particular embodiments, the PEG is PEG 3350, and the additive is caffeine. The present invention also relates to novel anti-human PD-1 mAb crystals produced by the methods described herein. Characterization of the resolubilized crystal suspensions using several biochemical methods indicates that the biophysical properties of the resolubilized mAb crystals are consistent with the intact antibody starting sample. The crystals and methods of the present invention are suitable for a variety of pharmaceutical applications, such as purification, storage, formulation, and drug delivery.

The invention provides methods for producing crystalline an anti-PD-1 monoclonal antibody (mAb), wherein the mAb is pembrolizumab or a pembrolizumab variant, comprising (1) mixing a solution comprising (a) the mAb, (b) polyethylene glycol (PEG), and (c) an additive selected from the group consisting of: caffeine, theophylline, 2′ deoxyguanosine-5′-monophosphate, a bioactive gibberellin, and a pharmaceutically acceptable salt of said bioactive gibberellin, to form a crystallization solution, (2) incubating the crystallization solution for a period of time sufficient for crystal formation; and (3) optionally harvesting the crystalline anti-PD-1 mAb from the solution. In specific embodiments, the PEG is PEG 3350 and the additive is caffeine. The invention also relates to the novel anti-human PD-1 mAb crystals produced by the methods described herein. Characterization of re-dissolved crystalline suspensions using several biochemical methods showed the bio-physical properties of the re-dissolved mAb crystals were consistent with the intact antibody starting sample. The crystals and methods of the invention are amenable to multiple pharmaceutical applications such as purification, storage, formulation, and drug delivery.

Disclosed herein are methods for treating classic Hodgkin lymphoma (cHL) in a subject in need thereof, comprising administering an IL-2 conjugate in combination with an anti-PD-1 antibody or antigen-binding fragment thereof.

The present disclosure provides a high-concentration composition of a PD-1 antibody and a method for preparing the same, which comprises pembrolizumab, wherein a portion of the pembrolizumab comprises a glucuronidation modification at the lysine at position 27 of the light chain of the amino acid sequence set forth in SEQ ID NO: 2, and wherein the content of the light chain of the pembrolizumab comprising the glucuronidation modification is less than or equal to 3% based on the percentage of the total content of the light chain of the pembrolizumab in the composition. The present disclosure also provides a pharmaceutical preparation comprising the above-mentioned composition. The present disclosure additionally provides a method for detecting the above-mentioned pembrolizumab comprising the glucuronidation modification and the use thereof in quality inspection or quality control of a product containing pembrolizumab.

The present invention relates to a method for enhancing productivity of clones for high level of expression of gene of interest by super transfection.