US2022378787A1PendingUtilityA1

Dosing of kras inhibitor for treatment of cancers

Assignee: AMGEN INCPriority: May 14, 2019Filed: Jul 22, 2022Published: Dec 1, 2022
Est. expiryMay 14, 2039(~12.8 yrs left)· nominal 20-yr term from priority
A61K 2300/00A61K 31/53A61K 31/519A61P 35/00A61K 31/505A61K 2039/505A61K 9/0053A61K 31/5377A61K 45/06A61K 31/5355
72
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Claims

Abstract

Provided herein are methods of administering a KRAS G12C inhibitor to a cancer subject.

Claims

exact text as granted — not AI-modified
What is claimed: 
     
         1 . A method of treating cancer comprising administering to a subject in need thereof Compound A in a daily dose of 180 mg, 360 mg, 720 mg, or 960 mg, wherein Compound A has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , wherein Compound A has the structure 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein Compound A has the structure 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of any one of  claims 1 ,  2  or  3 , wherein the cancer is a solid tumor. 
     
     
         5 . The method of any one of  claim 1 ,  2 ,  3  or  4 , wherein the cancer is non-small cell lung cancer. 
     
     
         6 . The method of any one of  claims 1 - 4 , wherein the cancer is colorectal cancer. 
     
     
         7 . The method of any one of  claims 1 - 4 , wherein the cancer is pancreatic cancer. 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein the cancer is a KRAS G12C mutated cancer. 
     
     
         9 . The method of any one of  claims 1  to  8 , wherein the subject, prior to start of Compound A therapy, had undergone at least one other systemic cancer therapy. 
     
     
         10 . The method of  claim 9 , wherein the subject had undergone at least two other systemic cancer therapies. 
     
     
         11 . The method of any one of  claims 1  to  9 , wherein Compound A is administered orally. 
     
     
         12 . The method of any one of  claims 1  to  11 , wherein the Compound A is administered as a single daily dose. 
     
     
         13 . The method of any one of  claims 1  to  12 , wherein the subject does not exhibit any grade 3 or grade 4 adverse events associated with Compound A therapy after administration of Compound A for at least 1 month. 
     
     
         14 . The method of  claim 13 , wherein the subject does not exhibit any grade 3 or grade 4 adverse events associated with Compound A therapy after administration of Compound A for at least 3 months. 
     
     
         15 . The method of any one of  claims 1  to  14 , wherein the Compound A dose is 180 mg. 
     
     
         16 . The method of any one of  claims 1  to  14 , wherein the Compound A dose is 360 mg. 
     
     
         17 . The method of any one of  claims 1  to  14 , wherein the Compound A dose is 720 mg. 
     
     
         18 . The method of any one of  claims 1  to  14 , wherein the Compound A dose is 960 mg. 
     
     
         19 . The method of any one of  claims 1  to  18 , wherein the subject is administered Compound A for at least one month. 
     
     
         20 . The method of any one of  claims 1  to  18 , wherein the subject is administered Compound A for at least three months. 
     
     
         21 . The method of any one of  claims 1  to  18 , wherein the subject is administered Compound A for at least six months. 
     
     
         22 . The method of any one of  claims 19  to  21 , wherein the subject exhibits at least a stable disease (SD). 
     
     
         23 . The method of  claim 22 , wherein the subject exhibits at least a partial response (PR). 
     
     
         24 . The method of any one of  claims 1  to  23 , wherein the subject does not exhibit a dose limiting toxicity (DLT). 
     
     
         25 . The method of any one of  claims 1  to  24 , wherein Compound A is as the M atropisomer. 
     
     
         26 . The method of any one of  claims 1  to  25 , further comprising administering to the subject a chemotherapeutic. 
     
     
         27 . The method of  claim 24 , wherein the chemotherapeutic comprises an anti-PD1 antibody. 
     
     
         28 . The method of  claim 25 , wherein the anti-PD1 antibody is Pembrolizumab (Keytruda), Nivolumab, AUNP-12, AMG 404, or Pidilizumab. 
     
     
         29 . The method of  claim 26 , wherein the chemotherapeutic comprises an anti-PDL1 antibody. 
     
     
         30 . The method of  claim 29 , wherein the anti-PDL1 antibody is Atezolizumab, MPDL3280A, Avelumab or Durvalumab. 
     
     
         31 . The method of  claim 26 , wherein the chemotherapeutic comprises a MEK inhibitor. 
     
     
         32 . The method of  claim 31 , wherein the MEK inhibitor is trametinib, pimasertib, PD-325901, MEK162, TAK-733, GDC-0973 or AZD8330. 
     
     
         33 . The method of  claim 26 , wherein the chemotherapeutic comprises a CDK4/6 inhibitor. 
     
     
         34 . The method of  claim 33 , wherein the CDK4/6 inhibitor comprises abemaciclib, or palbociclib. 
     
     
         35 . The method of  claim 26 , wherein the chemotherapeutic comprises a PI3K inhibitor. 
     
     
         36 . The method of  claim 35 , wherein the PI3K inhibitor comprises AMG 511 or buparlisib. 
     
     
         37 . The method of  claim 22 , wherein the stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. 
     
     
         38 . The method of  claim 23 , wherein the partial response is at least a 30% decrease in the sum of diameters of target lesions.

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