Pucotenlimab plus dose-intensified radiotherapy and chemotherapy for locally advanced rectal cancer: Preliminary results from a prospective, single-arm phase II trial (PUCRT).

Abstract

e15635 Background: The neoadjuvant PD-1 inhibitors plus chemoradiotherapy (nCRT) has improved complete response (CR) rates in patients with locally advanced rectal cancer (LARC). However, the optimal radiotherapy strategy—particularly whether simultaneous tumor-focused dose intensification can further potentiate immunotherapeutic efficacy—remains unclear. This study evaluates pucotenlimab combined with dose-intensified nCRT and explores whether this approach enhances tumor response and clinical outcomes in LARC. Methods: This prospective, single-arm phase II study enrolled patients with pMMR/MSS LARC (cT3–4 and/or N+, M0; tumor ≤10 cm from the anal verge). All participants received neoadjuvant, dose-intensified radiotherapy (57.5 Gy in 25 fractions) targeting the primary tumor and involved nodes, combined with concurrent capecitabine and pucotenlimab (anti-PD-1). This was followed by two cycles of consolidation therapy with pucotenlimab plus capecitabine and oxaliplatin (CAPOX). Based on treatment response and patient preference, patients underwent either radical surgery or a watch-and-wait (W&W) strategy. Subsequently, all patients completed four additional cycles of pucotenlimab plus CAPOX. The primary endpoint was complete response (CR), defined as either pathological CR (pCR) or clinical CR (cCR). Results: From August 2024 to December 2025, 36 patients were enrolled. 63.89% (23/36) cases with tumors were located ≤5 cm from the anal verge, including 38.89% (14/36) with ultra-low tumors (≤3cm). High-risk features (T4a/b, mesorectal fascia involvement, positive lateral lymph nodes, N2 disease, or extramural venous invasion) were present in 88.89% (32/36) of patients. At the data cutoff, 24 patients had completed response evaluation after consolidation therapy, 9 underwent surgery and 15 adopted a W&W strategy. The pCR rate among surgical patients was 55.56% (5/9). All 15 patients in the W&W group achieved cCR, resulting in an overall CR rate of 83.33% (20/24). Organ preservation was achieved in 62.50% (15/24) of all evaluable patientsand in 78.58% (11/14) among those with low rectal tumors. No treatment related death was reported. Conclusions: Pucotenlimab plus dose-intensified chemoradiotherapy achieved a high complete response rate with rapid tumor regression after just two consolidation cycles in patients with pMMR/MSS LARC, including those with high-risk and ultra-low tumors. This immunochemoradiotherapy regimen offers strong early tumor control and significant organ-preservation opportunity, particularly for very low rectal cancers. These promising findings warrant further validation in larger, comparative trials. Clinical trial information: NCT06770270 .