Results of phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with chemoradiotherapy in patients with rectal cancer

Aim: To evaluate the efficacy, recommended phase II dose (RP2D), dose-limiting toxicity (DLT), and safety profiles of PEP503 (NBTXR3) in combination with concurrent chemoradiotherapy (CCRT) in patients with locally advanced or unresectable rectal adenocarcinoma. Methods: A single administration of intratumor injection of PEP503 (NBTXR3) (multiple punctures) was applied, followed by radiotherapy in combination with capecitabine or 5-fluorouacil (5-FU). Surgery was performed 8 to 12 weeks after completion of CCRT. Results: Thirty-two patients were enrolled (one dropped out before CCRT), comprising 20 in phase Ib and 12 in phase II. The disease control rate was 100% (n = 31). One (3.2%) and 19 (61.3%) patients achieved clinical complete response and partial response, respectively. Twenty-five patients underwent surgery, of whom 24 (96%) had R0 resection and 5 (20%) had pathological complete response. Most of the adverse events were grade 1/2 events. Conclusion: Intratumor injection of PEP503 (NBTXR3) in patients with locally advanced or unresectable rectal adenocarcinoma is safe and effective. Addition of PEP503 (NBTXR3) to fluoropyrimidine-based neoadjuvant CCRT does not engender increased toxicity. The strong safety profile and encouraging efficacy of PEP503 (NBTXR3) in combination with neoadjuvant CCRT in locally advanced or unresectable rectal cancer warrant further examination in clinical studies. Clinical Trial registration: This study was registered on ClinicalTrials.gov Identifier: NCT02465593.