SUBCUTANEOUS DOSING OF ANTI-CD20/ANTI-CD3 BISPECIFIC ANTIBODIES

1 - 169 . (canceled)

170 . A method of reducing the rate of certain adverse events in a population of subjects having a non-Hodgkin's lymphoma (NHL) who are administered mosunetuzumab, the method comprising subcutaneously administering mosunetuzumab to each subject of the population in a step-dosing regimen comprising eight dosing cycles, wherein:

(a) the first dosing cycle comprises a first subcutaneous dose (C1D1), a second subcutaneous dose (C1D2), and a third subcutaneous dose (C1D3) of mosunetuzumab, wherein:

(i) the C1D1 is 5 mg;

(ii) the C1D2 is 45 mg; and

(iii) the C1D3 is 45 mg; and

(b) the second to eighth dosing cycles each comprises a single subcutaneous dose (C2D1-C8D1) of mosunetuzumab, wherein each of the C2D1-C8D1 of mosunetuzumab is 45 mg,

wherein the eight cycles are 21-day dosing cycles; or the first dosing cycle is a 21-day dosing cycle and the second to eighth dosing cycles are 28-day dosing cycles, and wherein the method comprises administering to each subject of the population the C1D1, the C1D2, and the C1D3 on or about Days 1, 8, and 15, respectively, of the first dosing cycle and administering to each subject of the population the C2D1-C8D1 on Day 1 of each of the second to eighth dosing cycles,

wherein the rate of certain adverse events is reduced in the population of subjects compared to a reference population of subjects to whom the mosunetuzumab is administered intravenously.

171 - 174 . (canceled)

175 . The method of claim 170 , wherein the dosing regimen comprises one or more additional dosing cycles.

176 . The method of claim 175 , wherein the dosing regimen comprises one to nine additional dosing cycles.

177 . (canceled)

178 . The method of claim 175 , wherein the dosing regimen comprises nine additional dosing cycles.

179 . The method of claim 175 , wherein each additional dosing cycle:

(a) is a 21-day dosing cycle or a 28-day dosing cycle; and/or

(b) comprises administration of an additional dose of mosunetuzumab.

180 - 182 . (canceled)

183 . The method of claim 179 , wherein:

(a) each additional dose of the bispecific antibody is about 45 mg; and/or

(b) the method comprises administering to each subject of the population each additional dose of the bispecific antibody on Day 1 of each respective additional dosing cycle.

184 - 186 . (canceled)

187 . The method of claim 170 , wherein the NHL is a previously untreated (1 L) NHL, a relapsed or refractory NHL, a diffuse-large B cell lymphoma (DLBCL), a follicular lymphoma (FL), a mantle cell lymphoma (MCL), a high-grade B cell lymphoma, an Ann Arbor stage III or IV NHL, or a primary mediastinal (thymic) large B cell lymphoma (PMLBCL).

188 . (canceled)

189 . The method of claim 187 , wherein the DLBCL is a Richter's transformation.

190 . (canceled)

191 . The method of claim 187 , wherein the FL is a transformed FL.

192 - 193 . (canceled)

194 . The method of claim 170 , wherein the rate of the cytokine release syndrome in the population of subjects after subcutaneous administration of the mosunetuzumab is less than or equal to about 30%, 25%, 10%, 5%, or 3%.

195 - 197 . (canceled)

198 . The method of claim 170 , wherein the rate of cytokine release syndrome having a grade of 2 or greater (as defined by the American Society for Transplantation and Cellular Therapy, 2018; ASTCT) in the population of subjects after subcutaneous administration of the mosunetuzumab is less than or equal to about 10%, 5%, 3%, or 1%; or is 0%.

199 - 202 . (canceled)

203 . The method of claim 170 , wherein after subcutaneous administration of the mosunetuzumab to each subject of the population, in the population of subjects:

(a) the complete response rate is at least about 20% or 40%;

(b) the median progression free survival is greater than about four months;

(c) the median overall survival is greater than about 9.5 months;

(d) the objective response rate at about 24 months after treatment was begun is at least about 70% or 75%; and/or

(e) the objective response rate at about 12 months after treatment was begun is at least about 60%.

204 - 209 . (canceled)

210 . The method of claim 170 , wherein the population of subjects has relapsed or refractory NHL, and wherein after subcutaneous administration of the mosunetuzumab to each subject of the population, in the population of subjects the objective response rate is:

(a) at least 34% or 44%;

(b) is between 35%-55%; or

(c) is about 45%.

211 - 213 . (canceled)

214 . The method of claim 170 , wherein the population of subjects has relapsed or refractory FL, and wherein after subcutaneous administration of the mosunetuzumab to each subject of the population, in the population of subjects the objective response rate is:

(a) at least 70% or 80%;

(b) between 70%-90%; or

(c) about 80%.

215 - 217 . (canceled)

218 . The method of claim 170 , wherein the population of subjects has relapsed or refractory DLBCL or transformed FL, and wherein after subcutaneous administration of the mosunetuzumab to each subject of the population, in the population of subjects the objective response rate is at least 25% or 35%.

219 . (canceled)

220 . The method of claim 170 , wherein the population of subjects has relapsed or refractory DLBCL, and wherein after subcutaneous administration of the mosunetuzumab to each subject of the population, in the population of subjects the objective response rate is between 25%-45%, or is about 35%.

221 - 255 . (canceled)

256 . The method of claim 170 , wherein mosunetuzumab is administered to the subjects as a monotherapy or as a combination therapy.

257 . The method of claim 170 , wherein mosunetuzumab is administered to the subjects concurrently with an additional therapeutic agent, prior to the administration of an additional therapeutic agent, or subsequent to the administration of one or more additional therapeutic agent.

258 . The method of claim 257 , wherein the additional therapeutic agent is obinutuzumab or tocilizumab.

259 . The method of claim 170 , wherein the subjects have a cytokine release syndrome event, and the method further comprises treating the symptoms of the cytokine release syndrome event while suspending treatment with mosunetuzumab.

260 . The method of claim 259 , wherein the method further comprises administering to the subjects an effective amount of tocilizumab and/or an effective amount of a corticosteroid to treat the cytokine release syndrome event.

261 . The method of claim 170 , wherein the subjects are human.

262 . The method of claim 170 , wherein the dosing regimen comprises one to nine additional dosing cycles, wherein each additional dosing cycle is a 21-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

263 . The method of claim 170 , wherein the dosing regimen comprises one to nine additional dosing cycles, wherein each additional dosing cycle is a 28-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

264 . The method of claim 170 , wherein the dosing regimen comprises nine additional dosing cycles, wherein each additional dosing cycle is a 21-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

265 . The method of claim 170 , wherein the dosing regimen comprises nine additional dosing cycles, wherein each additional dosing cycle is a 28-day dosing cycle, and wherein each additional dosing cycle comprises administration of an additional dose of 45 mg of mosunetuzumab on Day 1 of each respective additional dosing cycle.

266 . The method of claim 170 , wherein the subjects had previously been administered at least one prior line of systemic therapy.

267 . The method of claim 266 , wherein at least one prior line of systemic therapy comprised an anti-CD20 antibody or a Bruton's tyrosine kinase (BTK) inhibitor.

268 . The method of claim 267 , wherein the prior line of systemic therapy comprising the anti-CD20 antibody additionally comprises an alkylating agent, vincristine, fludarabine, or an anthracycline.