A phase IB/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

TPS3667 Background: Neoadjuvant chemoradiotherapy followed by surgical resection is the standard of care for locally advanced rectal cancer. There is strong interest in the development of novel agents and strategies to further improve the therapeutic ratio of chemoradiotherapy. One innovative approach is to incorporate nanoparticle (NP) therapeutics, which are known to preferentially accumulate in tumors. CRLX101 is a NP formulation of camptothecin (CPT), a potent nanotherapeutic shown to be safe in phase I clinical evaluation. In addition to inhibiting Topo-1, CRLX101 demonstrates durable suppression of HIF-1α, a regulator of the tumor survival pathway that was previously considered un-druggable. It has also been implicated in resistance to radiotherapy. Preclinically, CRLX101 has been shown to be a potent radiosensitizer. The purpose of this study is to evaluate whether the addition of CRLX101 to capecitabine and radiotherapy can improve pathologic complete response (pCR) and clinical outcomes for recta...