Safety and efficacy evaluation of neoadjuvant chemoradiotherapy plus thymalfasin and tislelizumab for treating MSS/pMMR locally advanced rectal cancer.

3587 Background: Neoadjuvant chemoradiotherapy is currently the standard strategy for microsatellite stable (MSS) / mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC) patients. This study aimed to explore the safety and efficacy of combining specific (thymalfasin) and non-specific (tislelizumab) tumor immunotherapy with chemoradiotherapy in MSS/pMMR LARC. Methods: This trial is an open, prospective, multi-center, single-arm phase II clinical study assessing the efficacy and safety of neoadjuvant chemoradiotherapy combined with thymosin andtislelizumab in MSS/pMMR LARC. Stage II/III MSS/pMMR LARC patients (cT 3-4a N 0 M 0 and cT 1-4a N 1-2 M 0 ) with the tumor distal location ≤ 10 cm from anal verge at two centers in China were consecutively enrolled. Patients received chemoradiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week, 5 weeks; plus capecitabine 850-1000 mg/m 2 , bid, po, 5 days/week, day1-5), thymalfasin (4.8 mg, biw, ih, day 1 and day 4 from week 1-11) and three 21-day cycles tislelizumab (200 mg, iv.gtt, week 2, 5 and 8) as neoadjuvant therapy. Adjuvant therapies after neoadjuvant were nonuniformly specified and decided according to clinical experiences. The primary endpoint is the complete response (CR) rate, defined as the achievement of clinical complete response (cCR) after neoadjuvant therapy or pathological complete response (pCR) after total mesorectal excision (TME). Results: From Feb 2024 to Aug 2024, a total number of patients (n = 25) were enrolled and 3 patients were excluded because of T4b and dMMR. Finally, 2 patients were discontinued and 20 completed neoadjuvant therapy. The median age was 67.5 (from 36 to 74) years while the median tumor distal location was6.0 (from 3.5 to 8.5) cm. The CR, PD, and SD rate was 40.0% (8/20), 45.0% (9/20), and 15.0% (3/20) correspondingly, with the ORR rate of 85.0% (17/20). Grade 3 treatment-related adverse events (trAEs) including leukopenia and neutropenia were observed in 1 (5%) patient, while grade 1-2 trAEs were observed in 15(75.0%) patients. As for Dec 31, 2024, the EFS rate was 100% (20/20) with median follow-up time of 18.57 weeks (from 6.86 to 31.86). Conclusions: Neoadjuvant chemoradiotherapy plus thymalfasin and tislelizumab show promising anti-tumour activity in MSS/pMMR LARC patients, with manageable toxicities. This study suggests that such combination could be a promising therapeutic strategy for patients with MSS/pMMR LARC. Clinical trial information: NCT06056804 .