Methods of treating cancer

Abstract

Provided are methods of treating cancer (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), HER2-positive gastric/gastroesophageal junction (GEJ) cancer, de novo or transformed diffuse large B cell lymphoma (DLBCL), or indolent lymphoma) in an individual that comprise administering to the individual (a) a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant, and (b) an anti-cancer antibody (e.g., an anti-PD1 antibody, anti-HER2 antibody, or an anti-CD20 antibody). Also provided are related kits pharmaceutical compositions.

1 - 13 . (canceled) 
     
     
         14 : A method of treating aggressive non-Hodgkin lymphoma (NHL) in an individual, comprising administering to the individual an effective amount of (a) a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant, and (b) an anti-CD20 antibody,
 wherein the SIRPα D1 domain variant comprises the amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 85; 
 wherein the Fc domain variant is
 (i) a human IgG1 Fc region comprising L234A, L235A, G237A, and N297A mutations, wherein numbering is according to the EU index of Kabat; 
 (ii) a human IgG2 Fc region comprising A330S, P331S, and N297A mutations, wherein numbering is according to the EU index of Kabat; 
 (iii) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, and delG236 mutations, wherein numbering is according to the EU index of Kabat; or 
 (iv) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, delG236, and N297A mutations, wherein numbering is according to the EU index of Kabat; and 
 
 wherein the aggressive NHL in the individual is relapsed and/or refractory to a prior treatment for aggressive NHL and there is no available curative therapy, and wherein the individual is a human. 
 
     
     
         15 : The method of  claim 14 , wherein the aggressive NHL is a diffuse large B-cell lymphoma (DLBCL). 
     
     
         16 : The method of  claim 15 , wherein the DLBCL is a de novo DLBCL or a transformed DLBCL. 
     
     
         17 : The method of  claim 14 , wherein the aggressive NHL is a mantle cell lymphoma (MCL). 
     
     
         18 : The method of  claim 14 , wherein the prior treatment for aggressive NHL comprised rituximab, cyclophosphamide, doxorubicin, vincristine, gemcitabine, lenalidomide, prednisone, prednisolone, etoposide, procarbazine, epirubicin, bendainustine, cisplatin, oxaliplatin, cytarabine, ifosfamide, carboplatir, dexamethasone, nesna, carmustine, melphalan, solumedrol methyl-glyoxal-bis(guanylhydrazone), thiotepa, methotrexate, ibrutinib, obinituzumab, tisagenlecleucel, axicabtagene, brentuximab vedotin, or combinations thereof. 
     
     
         19 : A method of treating indolent lymphoma in an individual, comprising administering to the individual an effective amount of (a) a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant, and (b) an anti-CD20 antibody,
 wherein the SIRPα D1 domain variant comprises the amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 85; 
 wherein the Fc domain variant is
 (i) a human IgG1 Fc region comprising L234A, L235A, G237A, and N297A mutations, wherein numbering is according to the EU index of Kabat; 
 (ii) a human IgG2 Fc region comprising A330S, P331S, and N297A mutations, wherein numbering is according to the EU index of Kabat; 
 (iii) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, and delG236 mutations, wherein numbering is according to the EU index of Kabat; or 
 (iv) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, delG236, and N297A mutations, wherein numbering is according to the EU index of Kabat; and 
 
 wherein the indolent lymphoma in the individual is relapsed and/or refractory to a prior treatment for indolent lymphoma, and wherein the individual is a human. 
 
     
     
         20 : The method of  claim 19 , wherein the indolent lymphoma is an indolent non-Hodgkin lymphoma (NHL). 
     
     
         21 : The method of  claim 20 , wherein the indolent NHL is a marginal zone lymphoma or a follicular lymphoma. 
     
     
         22 : The method of  claim 19 , wherein the prior treatment for indolent lymphoma comprised cyclophosphamide, doxorubicin, vincristine, gemcitabine, lenalidomide, prednisone, prednisolone, etoposide, procarbazine, epirubicin, bendamustine, cisplatin, oxaliplatin, cytarabine, ifosfamide, carboplatir, dexamethasone, mesna, carmustine, melphalan, solumedrol methyl-glyoxal-bis(guanylhydrazone), thiotepa, methotrexate, ibrutinib; rituximab, obinituzumab, tisagenlecleucel, axicabtagene, brentuximab vedotin, fludarabine mitoxantrone, everolimus, bortezomib, navitoclax, or combinations thereof. 
     
     
         23 : The method of  claim 14 , wherein the anti-CD20 antibody is rituximab. 
     
     
         24 : The method of  claim 23 , wherein rituximab is administered to the individual at a dose of 375 mg/m 2  by IV infusion, wherein rituximab is administered to the individual once per week for four weeks and once per month thereafter. 
     
     
         25 : The method of  claim 14 , wherein the SIRPα D1 domain variant comprises the amino acid sequence of SEQ ID NO: 85. 
     
     
         26 : The method of  claim 14 , wherein the SIRPα D1 domain variant comprises the amino acid sequence of SEQ ID NO: 81. 
     
     
         27 : The method of  claim 14 , wherein the Fc domain variant is a human IgG1 Fc region comprising L234A, L235A, G237A, and N297A mutations, wherein numbering is according to the EU index of Kabat. 
     
     
         28 : The method of  claim 27 , wherein the Fc domain variant comprises the amino acid sequence of SEQ ID NO: 91. 
     
     
         29 : The method of  claim 14 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant comprises the amino acid sequence of SEQ ID NO: 136. 
     
     
         30 : The method of  claim 14 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant comprises the amino acid sequence of SEQ ID NO: 135. 
     
     
         31 : The method of  claim 14 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant forms a homodimer. 
     
     
         32 : The method of  claim 14 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant is administered to the individual at a dose of 10 mg/kg once per week (QW). 
     
     
         33 : The method of  claim 14 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant is administered to the individual at a dose of 15 mg/kg once per week (QW). 
     
     
         34 : The method of  claim 14 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant is administered to the individual by IV infusion. 
     
     
         35 - 57 . (canceled) 
     
     
         58 : The method of any one of  claim 19 , wherein the anti-CD20 antibody is rituximab. 
     
     
         59 : The method of  claim 58 , wherein rituximab is administered to the individual at a dose of 375 mg/m 2  by IV infusion, wherein rituximab is administered to the individual once per week for four weeks and once per month thereafter. 
     
     
         60 : The method of  claim 19 , wherein the SIRPα D1 domain variant comprises the amino acid sequence of SEQ ID NO: 85. 
     
     
         61 : The method of  claim 19 , wherein the SIRPα D1 domain variant comprises the amino acid sequence of SEQ ID NO: 81. 
     
     
         62 : The method of  claim 19 , wherein the Fc domain variant is a human IgG1 Fc region comprising L234A, L235A, G237A, and N297A mutations, wherein numbering is according to the EU index of Kabat. 
     
     
         63 : The method of  claim 62 , wherein the Fc domain variant comprises the amino acid sequence of SEQ ID NO: 91. 
     
     
         64 : The method of  claim 19 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant comprises the amino acid sequence of SEQ ID NO: 136. 
     
     
         65 : The method of  claim 19 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant comprises the amino acid sequence of SEQ ID NO: 135. 
     
     
         66 : The method of  claim 19 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant forms a homodimer. 
     
     
         67 : The method of  claim 19 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant is administered to the individual at a dose of 10 mg/kg once per week (QW). 
     
     
         68 : The method of  claim 19 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant is administered to the individual at a dose of 15 mg/kg once per week (QW). 
     
     
         69 : The method of  claim 19 , wherein the polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant is administered to the individual by IV infusion.