Abstract 1306: A Phase 1b/2a study of CRLX101, a novel nanopharmaceutical of camptothecin, in solid tumor cancer patients who have failed standard therapy

Abstract

Abstract Results from a 24-patient dose-escalation safety and tolerability Phase 1 study of CRLX101 were presented at the 22nd EORTC-NCI-AACR symposium in November 2010. A Phase 2a expansion study of CRLX101 has been initiated to investigate the biological activity and tolerability in cancer patients with specific tumor types at the maximum-tolerated dose (MTD) of 15 mg/m2. Specifically, a focus of the Phase 2a expansion study is to evaluate CRLX101 biological activity in non-small cell lung carcinoma (NSCLC), amongst other target indications. In this Phase 2a expansion study, thirty-six (36) patients will be enrolled from three (3) clinical sites in the United States. Fifteen (15) patients treated with CRLX101 thus far were patients with advanced NSCLC. Stable disease of greater than 6 months in multiple NSCLC patients treated with CRLX101 has been observed. Dose-limiting bone marrow toxicities of thrombocytopenia and neutropenia were addressed with the longer dosing interval of an every-other-week dosing schedule, which accommodates for the prolonged half-life of CRLX101. Hemorrhagic cystitis, the classic camptothecin toxicity, has not been observed. No other significant adverse events have been observed in the current study. The Phase 2a study will be fully enrolled by the end of 2010 with extensive follow-up on most patients by April of 2011. All of the safety, tolerability, and biological activity data will be presented. At this time, twenty-one (21) of the thirty-six (36) patients have been enrolled. To date, three (3) NSCLC patients have received 4 cycles of therapy and are continuing on study. One (1) NSCLC patients is receiving the seventh cycle of therapy. A controlled, randomized Phase 2 study of CRLX101 in NSCLC is planned and will be initiated in early 2011. CRLX101's favorable tolerability profile may enable combination therapy with other cytotoxic drugs including carboplatin and gemcitabine without added toxicities. Preclinical data on the efficacy and tolerability of such combinations will also be presented. In addition, the dual activity of CRLX101 against both topoisomerase-1 and HIF1α suggest that combination with VEGF antagonists could be synergistic. Similarly, pre-clinical data on the dual mechanism inhibition by CRLX101 based on its pharmacokinetics will be presented. 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 1306. doi:10.1158/1538-7445.AM2011-1306