Figure 5. Antitumor efficacy of anetumab ravtansine in combination with doxorubicin/PLD or carboplatin in preclinical ovarian cancer models in vitro and in vivo.

(A) Combination of anetumab ravtansine with doxorubicin in OVCAR-8 cells in vitro. The activity was determined as additive based on the determined combination indices (CI) between 0.8 and 1.2 (n = 5). (B) OVCAR-8 cell lysates were analyzed for γH2AX, cleaved PARP1 and HSP90 by Western blot at the indicated time points. (C) Tumor growth in the OVCAR-8 ovarian cancer model (n = 8). Treatments were initiated 21 days after tumor cell inoculation. (D) Tumor growth in the Ov6668 ovarian cancer PDX model (n = 9). Treatments were initiated 21 days after tumor inoculation. (E) Tumor growth in the ST081 ovarian cancer PDX model (n = 8). Treatments were initiated when tumors reached a size of 125–250 mm³. Anetumab ravtansine (i.v.), PLD (i.v.) and/or carboplatin (i.v.) were administered as indicated by arrows. ARav, anetumab ravtansine; Doxo, doxorubicin.