Methods of treating cancer
AssigneeALX Oncology Inc.
InventorsJaume PONS, Hong WAN, Sophia RANDOLPH
Life of this patent
Estimating the term…
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.
Claims44
A method of treating non-small cell lung cancer (NSCLC) 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-PD-1 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 deG236 mutations, wherein numbering is according to the EU index of Kabat;
- or
- (iv) a human IgG4 Fc region comprising S228P, E233P, F234V, L235A, deG236, and N297A mutations, wherein numbering is according to the EU index of Kabat;
- and wherein the individual is a human.
(canceled)
A method of treating head and neck squamous cell carcinoma (HNSCC) 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-PD-1 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 HNSCC in the individual has progressed while on a prior platinum therapy or after the prior platinum therapy, and wherein the individual is a human.
(canceled)
A method of treating HER2-positive gastric/gastroesophageal junction (GEJ) cancer 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-HER2 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 gastric/GEJ cancer in the individual has progressed following a prior treatment with a fluoropyrimidine-based therapy and/or a prior treatment with an anti-HER2 antibody, and wherein the individual is a human.
(canceled)
(canceled)
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.
(canceled)
(canceled)
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.
(canceled)
(canceled)
(canceled)
A kit comprising a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant in a pharmaceutically acceptable carrier, for use in combination with pembrolizumab for treating non-small cell lung cancer (NSCLC) in an individual in need thereof,
- 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 individual is human.
(canceled)
A kit comprising a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant in a pharmaceutically acceptable carrier for use in combination with pembrolizumab for treating head and neck squamous cell carcinoma (HNSCC) in an individual in need thereof,
- 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 HNSCC in the individual has progressed while on a prior platinum therapy or after the platinum therapy, and wherein the individual is human.
(canceled)
A kit comprising a polypeptide comprising a SIRPα D1 domain variant and an Fe domain variant in a pharmaceutically acceptable carrier for use in combination with trastuzumab for treating HER2-positive gastric/gastroesophageal junction (GEJ) cancer in an individual in need thereof,
- 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 HER2-positive gastric/GEJ cancer in the individual has progressed following a prior fluoropyrimidine-based therapy or a prior treatment with an anti-HER2 antibody, and wherein the individual is human.
(canceled)
A kit comprising a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant in a pharmaceutically acceptable carrier for use in combination with rituximab for treating aggressive non-Hodgkin lymphoma (NHL) in an individual in need thereof,
- 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 human.
42-44. (canceled)
A kit comprising a polypeptide comprising a SIRPα D1 domain variant and an Fc domain variant in a pharmaceutically acceptable carrier, for use in combination with rituximab for treating indolent lymphoma in an individual in need thereof,
- 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 or refractory to a prior treatment for indolent lymphoma, and wherein the individual is human.
46-57. (canceled)
Dependencies are inferred from the claim text.