Abstract 2480: MI130004, a new antibody-drug conjugate, induces strong, long-lasting antitumor effect in HER2 expressing breast tumor models

Abstract

Abstract Background: Antibody-drug conjugates (ADC`s) have emerged as powerful tools for the treatment of cancer, combining the potency of cytotoxic molecules with the selectivity of antibodies targeted towards specific antigens. Marine compounds represent an interesting opportunity worth exploring as they possess the requirements needed to be considered promising payloads. The in vivo results obtained with a new ADC, MI130004, in HER2 expressing breast tumors are presented here. Materials and Methods: To evaluate the long lasting antitumor effect induced by MI130004, immunodefficient female mice were subcutaneously implanted with HER2 expressing breast lines namely, JIMT-1, BT-474 and MAXF574.Tumor (ca. 100 mm3) bearing animals were randomly allocated (Day 0) to receive MI130004 (10mg/kg), trastuzumab (30 or 10 mg/kg) or placebo (N = 8-10/group). Intravenous treatments were weekly administered for 5 consecutive weeks and then, tumor volume growth was recorded 2-3 times per week. For survival evaluation, time to endpoint was define as the time from Day 0 to death as a results of tumor growth (>2000 mm3) or any other cause (e.g., tumor necrosis). Statistical differences were assessed by Kaplan-Meier curves with the log rank test. The follow-up period was extended until 90 (MAXF574) or 120 days (JIMT-1 and BT-474) after the initiation day (Day 0). Then, surviving animals were sacrificed, tumor (or skin around the former tumor site) dissected free, formalin fixed and paraffin embedded for histopathology evaluations. Results: The treatment with MI130004 induced a long lasting antitumor effect with statistically significant increases in median survival time compared to either placebo (P = 0.0336, P = 0.0001 and P<0.0001 for BT-474, JIMT-1 and MAXF574, respectively) or trastuzumab treatments (P = 0.0005 and P<0.0001 for JIMT-1 and MAXF574, respectively). Seventy one percent of mice xenografted with JIMT-1 and treated with MI130004 survived up to Day 120. Out of them, 40% experienced a complete tumor remission (tumor < 63 mm3). All animals originally xenografted with BT-474 experienced complete tumor remissions by Day 120. On Day 90, 90.0% of the population xenografted with MAXF574 survived and 55.6% of these experienced complete tumor remission. Conclusions: The treatment with MI130004 on mice bearing HER2 expressing breast tumors resulted in strong, long lasting antitumor activity, including complete tumor remissions. These results strongly suggest that MI130004 is a new ADC with extraordinary therapeutic anti-cancer properties. Citation Format: Pablo M. Aviles, Maria Jose J. Guillen, Alberto Gallardo, Maria Virtudes Cespedes, Ramon Mangues, Heiner Fiebig, Natalie Hartman, Juan Manuel Dominguez, Luis Francisco Garcia, Carlos Galmarini, Carmen Cuevas. MI130004, a new antibody-drug conjugate, induces strong, long-lasting antitumor effect in HER2 expressing breast tumor models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2480. doi:10.1158/1538-7445.AM2015-2480