Figure 3.
Antitumor activity of TAK-981 combined with monoclonal antibodies in xenograft models. (A) Tumor volumes in Daudi-bearing mice treated with TAK-981 (7.5 mg/kg, biweekly), rituximab (3 mg/kg, weekly), and/or daratumumab (7.5 mg/kg, biweekly) as indicated for 3 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .001. (B) Tumor volumes in OCI-Ly10–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly) and/or rituximab (1 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .001. (C) Tumor volumes in OCI-Ly10–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly), obinutuzumab (Obi, 1 mg/kg, weekly), and/or rituximab (Rit, 1 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in a single experiment, 2-tailed unpaired Welch’s t test). (D) Tumor volumes in TMD8-bearing mice treated with TAK-981 (15 mg/kg, biweekly) and/or rituximab (3 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P = .08 (additive combination effect). (E) Tumor volumes in PHTX-166L–bearing mice treated with TAK-981 (5 mg/kg, weekly) and/or rituximab (5 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 6 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .05. (F) Tumor volumes in LP-1–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly) and/or daratumumab (2.5 mg/kg, biweekly) as indicated for 5 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .05. (G) Tumor volumes in OCI-Ly10–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly), rituximab (3 mg/kg, weekly), and/or rituximab with LALA-PG mutations (3 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in a single experiment, 2-tailed unpaired Welch’s t test). (H) Tumor volumes in OCI-Ly10–bearing mice were treated with TAK-981 (7.5 mg/kg, biweekly), rituximab (1 mg/kg, weekly), clodronate liposome (200 µL per mouse at a first dose and 100 µL per mouse at subsequent doses, biweekly), and/or anti-asialo GM1 (aASGM1, 0.25 mg per mouse, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in the representative study). Bar graphs show percent change in tumor volumes from baseline on the indicated day of measurement (individual value; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). *P < .05, **P < .01, ***P < .001. The number of mice achieved CR per the number of total mice in the group is shown. At least 2 similar experiments were performed unless otherwise specified. SD, standard deviation; N.S., not significant (P > .05).

Antitumor activity of TAK-981 combined with monoclonal antibodies in xenograft models. (A) Tumor volumes in Daudi-bearing mice treated with TAK-981 (7.5 mg/kg, biweekly), rituximab (3 mg/kg, weekly), and/or daratumumab (7.5 mg/kg, biweekly) as indicated for 3 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .001. (B) Tumor volumes in OCI-Ly10–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly) and/or rituximab (1 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .001. (C) Tumor volumes in OCI-Ly10–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly), obinutuzumab (Obi, 1 mg/kg, weekly), and/or rituximab (Rit, 1 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in a single experiment, 2-tailed unpaired Welch’s t test). (D) Tumor volumes in TMD8-bearing mice treated with TAK-981 (15 mg/kg, biweekly) and/or rituximab (3 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P = .08 (additive combination effect). (E) Tumor volumes in PHTX-166L–bearing mice treated with TAK-981 (5 mg/kg, weekly) and/or rituximab (5 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 6 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .05. (F) Tumor volumes in LP-1–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly) and/or daratumumab (2.5 mg/kg, biweekly) as indicated for 5 weeks (mean with SD; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). The P value of the synergy score was P < .05. (G) Tumor volumes in OCI-Ly10–bearing mice treated with TAK-981 (7.5 mg/kg, biweekly), rituximab (3 mg/kg, weekly), and/or rituximab with LALA-PG mutations (3 mg/kg, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in a single experiment, 2-tailed unpaired Welch’s t test). (H) Tumor volumes in OCI-Ly10–bearing mice were treated with TAK-981 (7.5 mg/kg, biweekly), rituximab (1 mg/kg, weekly), clodronate liposome (200 µL per mouse at a first dose and 100 µL per mouse at subsequent doses, biweekly), and/or anti-asialo GM1 (aASGM1, 0.25 mg per mouse, weekly) as indicated for 2 weeks (mean with SD; n = 8 mice per group in the representative study). Bar graphs show percent change in tumor volumes from baseline on the indicated day of measurement (individual value; n = 8 mice per group in the representative study, 2-tailed unpaired Welch’s t test). *P < .05, **P < .01, ***P < .001. The number of mice achieved CR per the number of total mice in the group is shown. At least 2 similar experiments were performed unless otherwise specified. SD, standard deviation; N.S., not significant (P > .05).

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal