Abstract 5359: Antitumor efficacy of EC1456 in patient derived xenograft models of ovarian, endometrial, NSCLC and TNBC

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.5359-5359
• Main Authors: Reddy, Joseph A., Bloomfield, Alicia, Taylor, Christina, Hargett, Katherine, Nelson, Melissa, Leamon, Christopher
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-5359

EC1456, a potent folate-targeted tubulysin conjugate, is currently being evaluated in a phase 1 dose escalation study in patients with advanced solid tumors. To assist in upcoming cancer indication selection decisions for advanced trials, we tested EC1456 against eight patient-derived xenograft (PDX) cancer models. Thus, EC1456 was evaluated as a single agent or in combination with standard of care (SOC) treatments against two folate receptor (FR)-positive models each of ovarian, endometrial, non-small cell lung (NSCLC) and triple negative breast (TNBC) tumor models. Nude mice engrafted subcutaneously with PDX tumors received 4 μmol/kg/week EC1456 for two weeks, following a once a week (SIW) or two times a week (BIW) schedules, either alone or in combination with 15 mg/kg, SIW x 2 Paclitaxel (ovarian and endometrial), 1 mg/kg SIW x 2 eribulin mesylate (TNBC) or 15 mg/kg, SIW docetaxel (NSCLC). EC1456 alone demonstrated tumor growth suppression or stasis in most of the tumor models and significantly greater anti-tumor activity (including cures) with no detectable increase in toxicity when tested in combination with the SOC agents. Overall, EC1456 significantly augmented the growth inhibitory effects of SOC treatments against all four PDX cancer indications examined, thus lending support to future clinical development of this novel FR-targeted agent. Citation Format: Joseph A. Reddy, Alicia Bloomfield, Christina Taylor, Katherine Hargett, Melissa Nelson, Christopher Leamon. Antitumor efficacy of EC1456 in patient derived xenograft models of ovarian, endometrial, NSCLC and TNBC. [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 5359. doi:10.1158/1538-7445.AM2015-5359