JPWO2020249693A5 - - Google Patents

Claims (15)

A pharmaceutical composition for use in a method of treating cancer in a patient, wherein the fusion protein of SEQ ID NO: 1 or at least 80% of the contiguous sequence of at least about 20 amino acids up to the full length of SEQ ID NO: 1 wherein the method subjects the patient to at least 80% sequence identity to the fusion protein of SEQ ID NO: 1 or a contiguous sequence of at least about 20 amino acids up to the full length of SEQ ID NO: 1 periodically subcutaneously administering a dose of an active fusion protein , wherein the periodic dosing is from about once every 3 days to about once every 60 days . Regular dosing about once every 3 days to about once every 21 days, optionally once every 3 days, once every 4 days, once every 7 days, every 14 days once, or once every 21 days ; and/or
The dose is about 0.1 mg to about 30 mg, optionally 1 mg, 3 mg, 6 mg, 10 mg, 15 mg, 20 mg, or 30 mg for the fusion protein of SEQ ID NO:1, or optionally about 0.1 mg to about 30 mg, or about 1 μg/kg to about 500 μg/kg, or a corresponding fixed dose based on adults of about 60 to about 70 kg or children of about 12 kg to about 50 kg or more,
The pharmaceutical composition according to claim 1. periodic subcutaneous administration results in a greater increase in circulating CD8+ T cells in the patient compared to daily subcutaneous administration ; optionally,
At least a 2-fold increase in circulating CD8+ T cells in the patient over baseline;
the ratio of CD8+ T cell expansion in the patient is greater than the ratio of CD4+ regulatory T cell (Treg) expansion; and/or
the ratio of increase in circulating CD8+ T cells in the patient is greater than the ratio of increase in circulating CD4+ regulatory T cells (Treg);
The pharmaceutical composition according to claim 1. the cancer to be treated is one or both of a solid tumor and a hematologic cancer, optionally
the solid tumor is carcinoma, sarcoma, or lymphoma;
reduction in the size of solid tumors;
the hematologic cancer is leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, and multiple myeloma; and/or
The cancer to be treated is renal cell carcinoma (RCC), lymphoma, melanoma, hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma of the head and neck (SCCHN) , breast cancer, pancreatic cancer, prostate cancer, colon and rectal cancer, bladder cancer, cervical cancer, thyroid cancer, esophageal cancer, mouth cancer, mesothelioma, and non-melanoma skin cancer ,
The pharmaceutical composition according to claim 1. Patients have a lower risk of T-cell exhaustion compared to daily subcutaneous or intravenous administration ;
the patient has a lower risk of capillary leak syndrome (CLS) or cytokine release syndrome (CRS) compared to daily subcutaneous or intravenous administration; and/or
patients have a lower risk of weight loss compared to daily subcutaneous or intravenous administration;
The pharmaceutical composition according to claim 1. The method further comprises co-administering to the patient a therapeutically effective amount of a therapeutic agent, optionally wherein the therapeutic agent is a PARP inhibitor, a cytotoxic agent, a chemotherapeutic agent, or an immune checkpoint protein inhibitor; 2. The pharmaceutical composition of claim 1, optionally wherein the immune checkpoint inhibitor inhibits the interaction of PD-1 and PD-L1, optionally wherein the immune checkpoint inhibitor is pembrolizumab. . the ratio of increase in IFNγ present in the patient's peripheral blood, serum, or plasma resulting from subcutaneous administration is at least about 2-fold greater , at least about 5-fold greater, or about 2. The pharmaceutical composition of claim 1, which is 2-fold to about 5-fold larger . wherein the ratio of increase in IL-6 present in the patient's peripheral blood, serum, or plasma as a result of subcutaneous administration is about 2-fold or less compared to intravenous administration of equivalent doses; Item 1. The pharmaceutical composition according to item 1. pembrolizumab is co-administered prior to, concurrently with, or following administration of the fusion protein of SEQ ID NO: 1 , optionally
pembrolizumab is co-administered with the fusion protein of SEQ ID NO: 1 in a separate composition;
Pembrolizumab is administered by IV injection or infusion in an amount of 200 mg;
pembrolizumab is administered on day 1 of administration of the fusion protein of SEQ ID NO: 1; and/or
pembrolizumab is administered about once a week or about once every three weeks;
7. Pharmaceutical composition according to claim 6 . The dose is provided as a pharmaceutical composition formulated for subcutaneous administration , optionally
The pharmaceutical composition is a stable aqueous solution ready for administration or the pharmaceutical composition is lyophilized, optionally the lyophilized pharmaceutical composition using a pharmaceutically acceptable vehicle suitable for injection. and/or
doses include about 1 mg to about 30 mg for the fusion protein of SEQ ID NO: 1, optionally about 1 mg, 3 mg, 10 mg, or 30 mg for the fusion protein of SEQ ID NO: 1;
The pharmaceutical composition according to claim 1. 2. The pharmaceutical composition of claim 1, wherein periodic subcutaneous administration results in a greater ratio of CD8+ T cells to CD4+ T _reg in the patient compared to daily subcutaneous administration. 9. The pharmaceutical composition of claim 8 , wherein the ratio of increase in IL-6 present in the patient's peripheral blood, serum, or plasma resulting from subcutaneous administration is less than the ratio of increase in IFNγ. 2. The pharmaceutical composition of claim 1 , wherein the method further comprises repeating administration of the fusion protein of SEQ ID NO: 1 if cancer recurs or a new cancer develops in the patient. 2. The pharmaceutical composition of Claim 1, wherein the method provides at least a partial response in the patient. The mean fold change from baseline in IFNγ present in the patient's peripheral blood, serum, or plasma that the method is greater than the mean fold change from baseline in IL-6 present in the patient's peripheral blood, serum, or plasma 2. The pharmaceutical composition of claim 1 , which provides a rate of