Abstract 1781: Lorvotuzumab mertansine (IMGN901) in combination with standard-of-care paclitaxel/carboplatin therapy is highly active in a preclinical xenograft model of ovarian cancer
Authors: Whiteman Kathleen R. , Johnson Holly A. , Xu Shanqin , Pinkas Jan , Lutz Robert J. 
Published: August 2014

The CD56-binding antibody-maytansinoid conjugate, lorvotuzumab mertansine (IMGN901), is currently being evaluated as monotherapy in patients with CD56-positive solid tumors including ovarian cancer, SCLC, and Merkel cell carcinoma. Encouraging results have recently been reported for this clinical trial, including 3 objective responses in second-line or later use (Woll, et al., ESMO 2010).

CD56 is expressed on approximately 57% of ovarian cancers, supporting the clinical investigation of lorvotuzumab mertansine for this malignancy. Lorvotuzumab mertansine has been shown to be active as a single-agent against CD56-positive ovarian xenograft tumors, including OVCAR-3 and COLO 720E (Whiteman, et al., AACR 2008). Despite the high response rate of ovarian cancer to the standard-of-care first-line paclitaxel/carboplatin chemotherapy (approximately 60%), more than 80% of patients will relapse within 24 months of starting this treatment. Although advances in diagnosis and treatment have improved outcomes, the 5-year overall survival rate for ovarian cancer is only about 45%. Consequently, there is an unmet clinical need for treatments achieving long-term responses as first-line or second-line therapies for ovarian cancer. The possibility of achieving durable responses with combination of lorvotuzumab mertansine plus paclitaxel/carboplatin therapy was investigated in a preclinical model of ovarian cancer.

The activity of lorvotuzumab mertansine in combination with the standard-of-care paclitaxel/carboplatin therapy was evaluated against COLO 720E ovarian xenografts in mice. The two dose levels of paclitaxel (10 or 20 mg/kg weekly × 3) plus carboplatin (100 mg/kg single injection) evaluated without lorvotuzumab mertansine were both active in this model, resulting in complete tumor regressions (CR) in 1 of 6 and 2 of 6 mice, respectively, with all tumors recurring during the study. Lorvotuzumab mertansine administered at a dose of 13 mg/kg weekly × 3 was active as a single agent, resulting in a CR in 1 of 6 mice which recurred during the study. Combination of lorvotuzumab mertansine with either dose level of paclitaxel/carboplatin resulted in CRs in all mice (6 of 6 mice/group), with no tumor recurrence during the study period (123 days).

The long-term CRs observed in a preclinical model of ovarian cancer suggest lorvotuzumab mertansine in combination with standard-of-care agents would be a promising combination treatment regimen to evaluate in the clinic due to its potential to achieve an increased response rate and more durable responses compared with standard-of-care agents alone, which could represent a significant therapeutic benefit to ovarian cancer patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1781. doi:10.1158/1538-7445.AM2011-1781