Methods of treating cancer in subjects having dysregulated lymphatic systems

Abstract

Provided herein is a method for treating cancer in a patient in need thereof, wherein said cancer has a tumor proportion score (TPS) for programmed death receptor-1 (PD-11) or programmed death-ligand-1 (PD-L1) of 50% or less and said patient is negative for lymphatic dysfunction, comprising administering a therapeutically effective amount of an antagonist for immune checkpoint inhibition.

What is claimed is: 
     
         1 . A method for treating cancer in a patient in need thereof, wherein said cancer has a tumor proportion score (TPS) for programmed death receptor-1 (PD-1) or programmed death-ligand-1 (PD-L1) of 50% or less and said patient is negative for lymphatic dysfunction, comprising administering a therapeutically effective amount of an antagonist for immune checkpoint inhibition. 
     
     
         2 . The method of  claim 1 , wherein the TPS is 30% or less. 
     
     
         3 . The method of  claim 2 , wherein the TPS is 10% or less. 
     
     
         4 . The method of any of  claims 1  to  3 , wherein the lymphatic dysfunction is lymphangitic carcinomatosis (LC). 
     
     
         5 . The method of any of  claims 1  to  4 , wherein the immune checkpoint inhibition has a target chosen from PD-1, PD-L1, CTLA-4, LAG3, TIM-2, CD47, KIR, TIM3, CD30, OX40, IDO, and ICOS. 
     
     
         6 . The method of  claim 5 , wherein the immune checkpoint inhibition targets PD-1 or PD-L1. 
     
     
         7 . The method of any of  claims 1  to  6 , wherein the antagonist is chosen from afatinib dimaleate, alectinib, bevacizumab, carboplatin, ceritinib, crizotinib, docetaxel, doxorubicin, erlotinib, etoposide, everolimus, gefitinib, gemcitabine, mechlorethamine, methotrexate, necitumumab, nivolumab, osimertinib, paclitaxel, paclitaxel albumin-stabilized nanoparticles, pembrolizumab, pemetrexed, ramucirumab, topotecan, vinorelbine, pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         8 . The method of  claim 7 , wherein the antagonist is chosen from bevacizumab, necitumumab, nivolumab, pembrolizumab, ramucirumab, pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         9 . The method of  claim 8 , wherein the antagonist is pembrolizumab or pharmaceutically acceptable salts thereof. 
     
     
         10 . The method of any of  claims 1  to  9 , wherein the cancer is chosen from lung cancer, breast cancer, a cancer of the gastrointestinal tract, a cancer of unknown origin, head and neck cancer, bladder cancer, prostate cancer, skin cancer, kidney cancer, a primary brain tumor, ocular tumor, sarcoma, a cancer of primary soft tissue, mesenchymal cancer, bone cancer, ovarian cancer, cervical cancer, a tumor of the lymphatic system, leukemia, mismatch repair deficient positive tumors (MMRD positive), mismatch repair deficient negative tumors (MMRD negative), and microsatellite (MSI) instability positive or negative cancers. 
     
     
         11 . The method of  claim 10 , wherein the cancer is lung cancer chosen from non-small cell lung cancer (NSCLC), squamous cell lung cancer, large cell lung cancer, small cell lung cancer, bronchogenic carcinoma, adenocarcinoma, neuroendocrine lung cancer, and bronchoalveolar lung cancer. 
     
     
         12 . The method of  claim 11 , wherein the cancer is breast cancer chosen from ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), lobular carcinoma (ILC), inflammatory breast cancer, lobular carcinoma in situ (LCIS), male breast cancer, Paget's disease of the nipple, and Phyllodes tumors of the breast. 
     
     
         13 . The method of  claim 10 , wherein the breast cancer is invasive ductal carcinoma chosen from tubular carcinoma of the breast, medullary carcinoma of the breast, mucinous carcinoma of the breast, papillary carcinoma of the breast, and cribriform carcinoma of the breast. 
     
     
         14 . The method of  claim 13 , wherein the cancer is breast cancer defined by hormone receptor status chosen from estrogen receptor positive, estrogen receptor negative, progesterone receptor positive, progesterone receptor negative, herceptin positive, herceptin negative, and combinations thereof. 
     
     
         15 . The method of  claim 13 , wherein the cancer is breast cancer defined by expression of a pre-defined set of genes chosen from mammaprint, oncotypeDX, intrinsic subtypes, and nanostring prosigna. 
     
     
         16 . The method of  claim 10 , wherein the cancer is a cancer of the gastrointestinal tract chosen from a tumor of the stomach, gastric cancer, duodenal cancer, small or large intestine cancer, colorectal cancer, anal cancer, liver cancer, pancreatic cancer, gall bladder cancer, cholangiocarcinoma, and neuroendocrine cancer. 
     
     
         17 . The method of  claim 10 , wherein the cancer is a skin cancer chosen from basal cell cancer, squamous cell cancer, and melanoma. 
     
     
         18 . The method of  claim 10 , wherein the cancer is kidney cancer chosen from renal cell cancer, papillary, and oncocytoma. 
     
     
         19 . The method of  claim 10 , wherein the cancer is a primary brain tumor, chosen from glioma, a tumor with gliomatous components, a tumor with neuronal components, a tumor with oligodendroglial components, oligodendroglioma, astrocytoma, and glioblastoma multiforme. 
     
     
         20 . The method of  claim 10 , wherein the cancer is a tumor of the lymphatic system selected form the group consisting of B cell lymphoma, T cell lymphoma, diffuse B cell lymphoma, and Hodgkin's lymphoma. 
     
     
         21 . The method of  claim 10 , wherein the cancer is leukemia chosen from acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia. 
     
     
         22 . The method of any of  claims 1  to  10 , wherein the cancer is lung cancer and the antagonist is chosen from afatinib dimaleate, alectinib, bevacizumab, carboplatin, ceritinib, crizotinib, docetaxel, doxorubicin, erlotinib, etoposide, everolimus, gefitinib, gemcitabine, mechlorethamine, methotrexate, necitumumab, nivolumab, osimertinib, paclitaxel, paclitaxel albumin-stabilized nanoparticles, pembrolizumab, pemetrexed, ramucirumab, topotecan, vinorelbine, pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         23 . The method of any of  claims 1  to  22 , wherein the cancer is advanced cancer or metastatic cancer. 
     
     
         24 . A method for treating lung cancer in a patient in need thereof, which cancer has a tumor proportion score for programmed death receptor-1 (PD-1) or programmed death-ligand-1 (PD-L1) of 30% or less and said patient is negative for lymphangitic carcinomatosis (LC), comprising administering a therapeutically effective amount of an antagonist for immune checkpoint inhibition targeting PD-1 or PD-L1. 
     
     
         25 . The method of  claim 22 , wherein the antagonist is chosen from bevacizumab, necitumumab, nivolumab, pembrolizumab, ramucirumab, pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         26 . The method of  claim 23 , wherein the antagonist is pembrolizumab or pharmaceutically acceptable salts thereof. 
     
     
         27 . The method of any of  claims 22  to  24 , wherein the lung cancer is chosen from non-small cell lung cancer (NSCLC), squamous cell lung cancer, large cell lung cancer, small cell lung cancer, bronchogenic carcinoma, adenocarcinoma, neuroendocrine lung cancer, and bronchoalveolar lung cancer. 
     
     
         28 . The method of any of  claims 22  to  25 , wherein the lung cancer is advanced cancer or metastatic cancer. 
     
     
         29 . A method for treating lung cancer in a patient in need thereof, which cancer has a tumor proportion score for programmed death receptor-1 (PD-1) or programmed death-ligand-1 (PD-L1) of 30% or less and said patient is negative for lymphangitic carcinomatosis (LC), comprising administering a therapeutically effective amount of pembrolizumab or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The method of  claim 27 , wherein the cancer is lung cancer chosen from non-small cell lung cancer (NSCLC), squamous cell lung cancer, large cell lung cancer, small cell lung cancer, bronchogenic carcinoma, adenocarcinoma, neuroendocrine lung cancer, and bronchoalveolar lung cancer. 
     
     
         31 . A method for treating cancer in a patient in need thereof, by determining if said cancer has a tumor proportion score for programmed death receptor-1 (PD-1) or programmed death-ligand-1 (PD-L1) of 30% or less and confirming said patient is negative for lymphatic dysfunction, then administering a therapeutically effective amount of an antagonist for immune checkpoint inhibition. 
     
     
         32 . A method for treating cancer in a patient in need thereof, wherein said cancer has a tumor proportion score for programmed death receptor-1 (PD-1) or programmed death-ligand-1 (PD-L1) of 30% or less by administering a therapeutically effective amount of an antagonist for immune checkpoint inhibition. 
     
     
         33 . The method of  claim 30 , wherein the antagonist is pembrolizumab.