Neoadjuvant tislelizumab plus chemotherapy in MSS/pMMR high-risk locally advanced colon cancer: Updated analysis results from a phase 2 trial.

3638 Background: Patients with locally advanced colon cancer (LACC) have a poor prognosis, and those with N+ or T4 staging are prone to developing metastases. Only about 5% pathological complete response rates were observed in neoadjuvant chemotherapy. We conducted a single-arm, phase II trial to evaluate the efficacy and safety of immunotherapy combined with chemotherapy in locally advanced colon cancer. Methods: LACC patients clinically staged as T4 or N2 with histologically confirmed microsatellite stable/mismatch repair proficient (MSS/pMMR) type untreated colon adenocarcinoma are eligible for enrollment. Participants received 2-6 cycles of neoadjuvant therapy consisting of capecitabine and oxaliplatin (CAPOX) plus tislelizumab, followed by complete mesocolic excision. The primary endpoint was the pathological complete response (pCR) rate. This study was registered at ClinicalTrials.gov (NCT06124378). Results: A total of 61 patients were enrolled with a median age of 54 years (IQR 43–62). 35 (57%) of the recruited patients had a cT4 tumor and 47 (77%) of the patients had N2. All patients received neoadjuvant CAPOX plus tislelizumab, while three patients were excluded from activity analyses due to adverse events and the patient decision. Among the remaining 58 patients, 16 (28%) patients received 2 cycles, 39 (67%) patients completed 4 cycles, and 3 patients (5%) received 6 cycles prior to surgery. 14% patients achieved clinical complete response and the overall response rate was 91% based on clinical efficacy, with no cases of progressive disease observed. The regimen achieved a pathological complete response (pCR) rate of 41.4%, with all patients undergoing R0 resection. The major pathological response rate was 51.7% (95% CI 38.6 to 64.6). In subgroup analyses, patients with right-sided tumors exhibited higher pCR rates (16 47%, 95% CI 30–65 of 34, compared to 8 33%, 95% CI 17–54 of 24 for left-sided cases. However, no statistically significant differences were observed between the subgroups. Treatment-related adverse events of any grade occurred in 52 (85.2%) of 61 patients. The most common adverse events were peripheral sensory neurotoxicity (37 61% of 61) and decreased appetite (31 51%). Grade 3 drug-related serious adverse events occurred in 8 (13%) patients while no grade 4–5 adverse events occurred. Conclusions: This prospective trial demonstrates that neoadjuvant tislelizumab plus CAPOX provides a promising treatment strategy with encouraging antitumor activity and a manageable safety profile for MSS/pMMR locally advanced colon cancer. Clinical trial information: NCT06124378 .