Combination of lurbinectedin and immune checkpoint inhibitor

Abstract

Described are combination therapies for the treatment of solid tumours, said therapies comprising lurbinectedin and an immune checkpoint inhibitor, for example, anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies.

1 . A method of treatment of a solid tumour, the method comprising administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof, thereby treating the solid tumour. 
     
     
         2 . The method of  claim 1 , wherein the immune checkpoint inhibitor comprises an immunoglobulin molecule, preferably an antibody, targeting an immune checkpoint molecule. 
     
     
         3 . The method of  claim 2 , wherein the immune checkpoint molecule is selected from CTLA-4, PD-1, and PD-L1. 
     
     
         4 . The method of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a plurality of inhibitors targeting a plurality of immune checkpoint molecules, preferably CTLA-4 and PD-1. 
     
     
         5 . The method of any one of the preceding claims wherein the immune checkpoint inhibitor comprises a monoclonal antibody which specifically binds CTLA-4, or which specifically binds PD-1, or which specifically binds PD-L1. 
     
     
         6 . The method of  claim 5  wherein the monoclonal antibody is selected from pembrolizumab, nivolumab, ipilimumab, avelumab, atezolizumab, durvalumab, cemiplimab (REGN2810), camrelizumab (SHR1210), envafolimab (KN035), sintilimab (1131308), spartalizumab (PDR001), tislelizumab (BGB-A317), prolgolimab (BCD-100), toripalimab (JS001), dostarlimab (TSR-042, WBP-285) and tremelimumab (ticilimumab, CP-675,206). 
     
     
         7 . The method of any preceding claim wherein the lurbinectedin and the immune checkpoint inhibitor are administered concurrently, separately or sequentially. 
     
     
         8 . The method of  claim 7  wherein the lurbinectedin is administered initially, followed by the immune checkpoint inhibitor. 
     
     
         9 . The method of any preceding claim wherein multiple administrations of either the lurbinectedin, or the immune checkpoint inhibitor, or both, are given. 
     
     
         10 . The method of any preceding claim, wherein lurbinectedin is administered by intravenous infusion. 
     
     
         11 . The method of any preceding claim, wherein the immune checkpoint inhibitor is administered by intravenous infusion. 
     
     
         12 . The method of any preceding claim wherein the solid tumour is selected from the group consisting of prostate cancer, breast cancer, lung cancer, colorectal cancer, melanomas, bladder cancer, brain/CNS cancer, cervical cancer, oesophageal cancer, gastric cancer, head/neck cancer, kidney cancer, liver cancer, lymphomas, ovarian cancer, pancreatic cancer, and sarcomas. 
     
     
         13 . The method of any preceding claim, wherein the solid tumour is a lung cancer, melanoma, or is breast cancer. 
     
     
         14 . The method of any preceding claim, wherein the solid tumour expresses PD-L1. 
     
     
         15 . The method of any preceding claim, wherein the method further comprises determining whether the tumour to be treated expresses PD-L1 prior to beginning treatment. 
     
     
         16 . The method of any preceding claim, wherein the treatment results in one or more of: reduction in tumour size; delay in growth of tumour; prolongation of life of the patient; delay in disease progression; remission. 
     
     
         17 . A method of prolonging survival of a patient having a solid tumour, the method comprising administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof, thereby prolonging survival of the patient. 
     
     
         18 . A method of delaying disease progression of a solid tumour in a patient, the method comprising administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof, thereby delaying disease progression of the solid tumour. 
     
     
         19 . A method of reducing or delaying growth of a solid tumour, the method comprising administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof, thereby reducing or delaying growth of the solid tumour. 
     
     
         20 . A method of selecting a patient having a solid tumour for combination therapy, the method comprising determining whether the solid tumour expresses PD-L1, and if so, selecting the patient for combination therapy wherein the combination therapy comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor. 
     
     
         21 . The method of  claim 20 , further comprising providing said combination therapy to the patient. 
     
     
         22 . Use of lurbinectedin in the manufacture of a medicament for the treatment of a solid tumour, wherein said treatment comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof. 
     
     
         23 . Use of an immune checkpoint inhibitor in the manufacture of a medicament for the treatment of a solid tumour, wherein said treatment comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof. 
     
     
         24 . Use of lurbinectedin and an immune checkpoint inhibitor in the manufacture of a medicament for the treatment of a solid tumour, wherein said treatment comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof. 
     
     
         25 . Lurbinectedin for use in a method of treatment of a solid tumour, wherein said treatment comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof. 
     
     
         26 . An immune checkpoint inhibitor for use in a method of treatment of a solid tumour, wherein said treatment comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof. 
     
     
         27 . Lurbinectedin and an immune checkpoint inhibitor for use in a method of treatment of a solid tumour, wherein said treatment comprises administering a combination therapy of lurbinectedin and an immune checkpoint inhibitor to a patient in need thereof. 
     
     
         28 . A pharmaceutical package comprising lurbinectedin and an immune checkpoint inhibitor.