Neoadjuvant long-course chemoradiation plus PD1 blockade for locally advanced rectal cancer: Results of a phase 2, open-label, randomized controlled trial.

3611 Background: Several single-arm trials have reported pathological complete response (pCR) rates of 23-50% after combining neoadjuvant radiotherapy with immune checkpoint inhibitors in locally advanced rectal cancer (LARC). We aim to further clarify the efficacy and safety of adding PD1 inhibitors to the neoadjuvant long-course chemoradiation of LARC patients with this phase 2, randomized, controlled trial. Methods: Patients with mid-low, locally advanced rectal cancer were randomly allocated to receive neoadjuvant chemoradiation plus concurrent Tislelizumab (experiment group A), or neoadjuvant chemoradiation plus sequential Tislelizumab (experiment group B), or neoadjuvant chemoradiation only (control group). Patients of all three groups are scheduled to receive radical surgery after neoadjuvant treatment. The primary endpoint is pCR rate. Results: A total of 186 patients were enrolled. In the modified intention-to-treat population, which consist of patients having received chemoradiation and at least 1 cycle of PD1 blockade for the experiment groups and patients having received chemoradiation only for the control group, the pCR rates were 33.9% and 34.5% for experiment group A and B respectively, both significantly higher than the pCR rate of 15.5% in the control group (p=0.021 and 0.019). There were no significant differences between either one of the experiment groups and the control group regarding disease progression rate, grade 3-4 treatment-related adverse event rate and grade 3-4 surgical complication rate. Conclusions: For patients with mid-low locally advanced rectal cancer, the addition of PD1 inhibitors to neoadjuvant long-course chemoradiation, whether concurrently or sequentially, increases pCR rate, meanwhile raises no significant safety concerns. For the next step, phase 3 trials with larger sample sizes are encouraged. Clinical trial information: NCT05245474 .