542P - Long-term outcomes of neoadjuvant toripalimab with or without celecoxib in patients with dMMR/MSI-H locally advanced colorectal cancer: 3-month treatment cohort of the randomized phase II PICC trial

Background

Neoadjuvant PD-1 blockade has shown a high pathologic complete response (pCR) rate in patients with dMMR/MSI-H, locally advanced colorectal cancer (CRC). However, there is a lack of long-term survival data from prospective studies. Here, we report the 3-year oncologic outcomes from the 3-month treatment cohort of the PICC trial (NCT03926338).

Methods

The PICC study was a multi-cohort, randomized, phase 2 trial. Patients with clinical T3-4 and/or N+, and dMMR/MSI-H CRC were enrolled in the 3-month cohort and randomly assigned (1:1) to receive toripalimab 3 mg/kg, with or without celecoxib 200 mg twice daily from day 1 to 14 of each 14-day cycle, for 6 cycles before surgery. The primary endpoint of the pCR rate was met, showing significant improvement with neoadjuvant toripalimab with or without celecoxib compared to historical controls. Secondary endpoints included long-term oncologic outcomes. The data cutoff for this analysis was April 12, 2024.

Results

Between May 2019 and April 2022, 43 patients were included in the 3-month cohort (23 in the toripalimab plus celecoxib group and 24 in the toripalimab monotherapy group), with 34 enrolled for the primary objective and 13 for translational research. All 43 patients had an R0 resection. The pCR rate was 87% (95%CI, 70-96) in the toripalimab plus celecoxib group and 75% (95%CI, 57-88) in the toripalimab monotherapy group. At a median follow-up of 39 months, one case of second breast cancer, one death from postoperative abdominal infection, and one death from COVID-19 occurred in the monotherapy group. No events or deaths were reported in the toripalimab plus celecoxib group. The 3-year EFS and DFS rates were 100% in the toripalimab plus celecoxib group and 85% (95% CI, 71-99) in the monotherapy group. The 3-year OS rates were 100% and 91% (95% CI, 79-99), respectively. The 3-year cancer-specific survival rates were 100% and 96% (95% CI, 88-99).

Conclusions

This secondary analysis of the PICC trial showed 3-month neoadjuvant toripalimab, with or without celecoxib, resulted in promising long-term outcomes for dMMR/MSI-H locally advanced CRCs.

Clinical trial identification

ClinicalTrials.gov, NCT03926338.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The National Key R&D Program of China, the National Natural Science Foundation of China, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research.

Disclosure

All authors have declared no conflicts of interest.