Short-course radiotherapy and subsequent CAPOX plus camrelizumab followed by delayed surgery for locally advanced rectal cancer:Short-term results of a phase II trial.

63 Background: Chemoradiotherapy followed by radical surgery is standard treatment for patients with locally advanced rectal cancer (LARC). Short-course radiotherapy (SCRT), either with immediate or delayed surgery, provides similar oncological results compared with long-course radiotherapy with delayed surgery. Delayed surgery with the addition of neoadjuvant immunotherapy may bring better downstaging effect and minimize the risk of distant relapse. We conducted this single-arm phase 2 trial to investigate the efficacy and safety of SCRT combined with subsequent capecitabine and oxaliplatin (CAPOX) plus Camrelizumab (anti-PD-1 antibody) followed by delayed surgery in patients with LARC. Methods: Patients with histologically confirmed T3–4N0M0 or T1-4N+M0 rectal cancer, previously untreated disease, and ECOG performance status of 0-1, received SCRT (5×5 Gy) with subsequent two 21-day cycles of CAPOX (oxaliplatin 130 mg/m2 ivgtt, d1; capecitabine 1000 mg/m2 po bid, d1-14) plus Camrelizumab (200 mg iv drip, d1) after 1 week, followed by radical surgery after 1 week. Adjuvant therapy was decided by the investigator. The primary endpoint was pathological complete response (pCR) rate, defined as the absence of viable tumor cells in the primary tumor and lymph nodes. The study is ongoing to follow up the survival outcomes and obtain the results of next generation sequencing and PD-L1 expression. The data cutoff date was September 8, 2020. Results: From November 2019 to September 2020, a targeted number of patients (n = 29) were enrolled and are expected to complete the surgery by November 2020. The median age was 57 (range 31-73) years, 55% (16/29) of patients had ECOG performance status of 1, and the median distance from tumor to the anal verge was 5 (range, 1.9-9) cm. At data cutoff, 10 patients had undergone the surgery, with R0 resection rate of 100%. The pCR rate was 60% (6/10), including 56% (5/9) for those with mismatch repair-proficient, and 100% (1/1) for those with mismatch repair-deficient. Of 4 patients without pCR, 2 only received one cycle of CAPOX plus Camrelizumab due to the outbreak of COVID-19 in Wuhan, and 1 had signet-ring cell rectal carcinoma. At data cutoff, 20 patients had received at least one dose of Camrelizumab. Immune-related adverse events (irAEs) were all grade 1-2, and the most common irAE was reactive cutaneous capillary endothelial proliferation in 10 (50%) of 20 patients. Postoperative bleeding and infection occurred in 1 (10%) and 2 (20%) of 10 patients, respectively. No treatment-related death was observed. Conclusions: SCRT combined with subsequent CAPOX plus Camrelizumab followed by delayed surgery showed promising pCR rate with good tolerance in patients with LARC, regardless of the mismatch repair status, suggesting a candidate strategy for the neoadjuvant therapy. Clinical trial information: NCT04231552.