DOSING FOR COMBINATION TREATMENT WITH ANTI-CD20/ANTI-CD3 BISPECIFIC ANTIBODY AND ANTI-CD79B ANTIBODY DRUG CONJUGATE

1 .- 166 . (canceled)

167 . A method of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject polatuzumab vedotin and glofitamab in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle, wherein:

(a) the first dosing cycle comprises:

(i) a single dose (C1D1) of polatuzumab vedotin, wherein the C1D1 of polatuzumab vedotin is about 1.8 mg/kg; and

(ii) a first dose (C1D1) of glofitamab and a second dose (C1D2) of glofitamab, wherein the C1D1 of glofitamab is about 2.5 mg, and the C1D2 of glofitamab is about 10 mg; and

(b) the second dosing cycle comprises:

(i) a single dose (C2D1) of polatuzumab vedotin, wherein the C2D1 of polatuzumab vedotin is about 1.8 mg/kg; and

(ii) a single dose (C2D1) of glofitamab, wherein the C2D1 of glofitamab is about 30 mg, and wherein the dosing regimen further comprises administering to the subject rituximab, cyclophosphamide, doxorubicin, and a corticosteroid.

168 . The method of claim 167 , wherein:

(a) the dosing cycles are 21-day dosing cycles;

(b) glofitamab is administered intravenously; and/or

(c) polatuzumab vedotin is administered intravenously.

169 . The method of claim 167 , wherein the CD20-positive cell proliferative disorder is a B cell proliferative disorder.

170 . The method of claim 169 , wherein the B cell proliferative disorder is a B cell lymphoma.

171 . The method of claim 170 , wherein the B cell lymphoma is a diffuse-large B cell lymphoma (DLBCL), a high-grade B cell lymphoma (HGBCL), a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), or a transformed follicular lymphoma.

172 . The method of claim 171 , wherein the DLBCL is DLBCL, not otherwise specified (NOS).

173 . The method of claim 167 , wherein rituximab, cyclophosphamide, doxorubicin, and the corticosteroid are first administered to the subject prior to the first dosing cycle.

174 . The method of claim 167 , wherein polatuzumab vedotin is first administered to the subject prior to the first dosing cycle.

175 . The method of claim 167 , wherein the C1D1 of polatuzumab vedotin is administered on Day 2 (±1 day) of the first dosing cycle; and/or wherein the C2D1 of polatuzumab vedotin is administered on Day 1 (±1 day) of second first dosing cycle.

176 . A method of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject polatuzumab vedotin and glofitamab in a dosing regimen comprising seven 21-day dosing cycles, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) of glofitamab administered on Day 8 of the first dosing cycle, a second dose (C1D2) of glofitamab administered on Day 15 of the first dosing cycle, and a single dose (C1D1) of polatuzumab vedotin administered on Day 2 (±1 day) of the first dosing cycle, wherein the C1D1 of glofitamab is about 2.5 mg, and the C1D2 of glofitamab is about 10 mg;

(b) the second to fifth dosing cycles each comprises a single dose (C2D1-C 5 D1) of glofitamab and a single dose (C2D1-C5D1) of polatuzumab vedotin; and

(c) the sixth and seventh dosing cycles each comprises a single dose (C6D1-C7C1) of glofitamab and does not comprise administration of polatuzumab vedotin,

wherein each single dose C2D1-C7D1 of glofitamab is about 30 mg and each single dose C1D1-C5D1 of polatuzumab vedotin is about 1.8 mg/kg,

and wherein the dosing regimen further comprises administering to the subject rituximab, cyclophosphamide, doxorubicin, and a corticosteroid.

177 . The method of claim 176 , wherein the CD20-positive cell proliferative disorder is a B cell proliferative disorder.

178 . The method of claim 177 , wherein the B cell proliferative disorder is a B cell lymphoma.

179 . The method of claim 178 , wherein the B cell lymphoma is a diffuse-large B cell lymphoma (DLBCL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), or a transformed follicular lymphoma.

180 . The method of claim 176 , wherein rituximab, cyclophosphamide, doxorubicin, and the corticosteroid are first administered to the subject prior to the first dosing cycle.

181 . The method of claim 176 , wherein polatuzumab vedotin is first administered to the subject prior to the first dosing cycle.

182 . A method of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject polatuzumab vedotin and glofitamab in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle, wherein:

(a) the first dosing cycle comprises:

(i) a single dose (C1D1) of polatuzumab vedotin administered on Day 2 (±1 day) of the first dosing cycle; and

(ii) a first dose (C1D1) of glofitamab administered on Day 8 (±1 day) of the first dosing cycle and a second dose (C1D2) of glofitamab administered on Day 15 (±1 day) of the first dosing cycle, wherein the C1D1 of glofitamab is about 2.5 mg, and the C1D2 of glofitamab is about 10 mg; and

(b) the second dosing cycle comprises:

(i) a single dose (C2D1) of polatuzumab vedotin administered on Day 1 (±1 day) of the second dosing cycle; and

(ii) a single dose (C2D1) of glofitamab administered on Day 1 (±1 day) of the second dosing cycle, wherein the C2D1 of glofitamab is about 30 mg, and the C1D1 and C2D1 of polatuzumab vedotin are each about 1.8 mg/kg,

and wherein the dosing regimen further comprises administering to the subject rituximab.

183 . The method of claim 182 , wherein:

(a) the dosing cycles are 21-day dosing cycles;

(b) glofitamab is administered intravenously; and/or

(c) polatuzumab vedotin is administered intravenously.

184 . The method of claim 182 , wherein the method further comprises administering to the subject obinutuzumab.

185 . The method of claim 184 , wherein obinutuzumab is administered:

(a) prior to administration of glofitamab; and/or

(b) as a single dose of about 1000 mg.

186 . The method of claim 185 , wherein obinutuzumab is administered about seven days prior to administration of glofitamab.

187 . The method of claim 182 , wherein the CD20-positive cell proliferative disorder is a B cell proliferative disorder.

188 . The method of claim 187 , wherein the B cell proliferative disorder is a non-Hodgkin's lymphoma (NHL) or a central nervous system lymphoma (CNSL).

189 . The method of claim 188 , wherein the NHL is a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a mantle cell lymphoma (MCL), a marginal zone lymphoma (MZL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), a diffuse B cell lymphoma, or a small lymphocytic lymphoma.

190 . The method of claim 189 , wherein the FL is a transformed FL.

191 . The method of claim 188 , wherein the NHL is an aggressive NHL (aNHL).

192 . The method of claim 182 , wherein rituximab is administered about 1 day (±1 day) before administration of glofitamab.

193 . A method of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject polatuzumab vedotin and glofitamab in a dosing regimen comprising twelve 21-day dosing cycles, wherein:

(a) the first dosing cycle comprises a first dose (C1D1) of glofitamab administered on Day 8 (±1 day) of the first dosing cycle, a second dose (C1D2) of glofitamab administered on Day 15 (±1 day) of the first dosing cycle, and a single dose (C1D1) of polatuzumab vedotin administered on Day 2 (±1 day) of the first dosing cycle, wherein the C1D1 of glofitamab is about 2.5 mg, and the C1D2 of glofitamab is about 10 mg;

(b) the second to sixth dosing cycles each comprises a single dose (C2D1-C6D1) of glofitamab and a single dose (C2D1-C6D1) of polatuzumab vedotin; and

(c) the seventh to twelfth dosing cycles each comprises a single dose (C7D1-C12D1) of glofitamab and does not comprise administration of polatuzumab vedotin,

wherein each single dose C2D1-C12D1 of glofitamab is administered on Day 1 (±1 day) of each dosing cycle, and each single dose C1D1-C6D1 of polatuzumab vedotin is administered on Day 1 (±1 day) of each dosing cycle, and wherein each single dose C2D1-C12D1 of glofitamab is about 30 mg and each single dose C1D1-C6D1 of polatuzumab vedotin is about 1.8 mg/kg,

and wherein the dosing regimen further comprises administering to the subject rituximab.

194 . The method of claim 193 , wherein the CD20-positive cell proliferative disorder is a B cell proliferative disorder.

195 . The method of claim 194 , wherein the B cell proliferative disorder is a non-Hodgkin's lymphoma (NHL) or a central nervous system lymphoma (CNSL).

196 . The method of claim 195 , wherein the NHL is a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a mantle cell lymphoma (MCL), a marginal zone lymphoma (MZL), a high-grade B cell lymphoma, a primary mediastinal (thymic) large B cell lymphoma (PMLBCL), a diffuse B cell lymphoma, or a small lymphocytic lymphoma.

197 . The method of claim 196 , wherein the FL is a transformed FL.

198 . The method of claim 195 , wherein the NHL is an aggressive NHL (aNHL).

199 . The method of claim 193 , wherein rituximab is administered about 1 day (±1 day) before administration of glofitamab.

200 . The method of claim 193 , wherein the method further comprises administering to the subject obinutuzumab.

201 . The method of claim 200 , wherein obinutuzumab is administered:

(a) prior to administration of glofitamab; and/or

(b) as a single dose of about 1000 mg.

202 . The method of claim 201 , wherein obinutuzumab is administered about seven days prior to administration of glofitamab.

203 . The method of claim 200 , wherein the subject is administered a first dose of obinutuzumab of about 1000 mg about seven days prior to administration of the C1D1 of glofitamab.

204 . The method of claim 167 , wherein the corticosteroid is prednisone, prednisolone, or methylprednisolone.

205 . The method of claim 176 , wherein the corticosteroid is prednisone, prednisolone, or methylprednisolone.