Long-term neoadjuvant chemoradiotherapy combined with camrelizumab for locally advanced rectal cancer: A single-arm, prospective, phase II clinical study.

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Background: Neoadjuvant chemoradiotherapy (nCRT) has brought out a higher rate of complete response and anal sphincter preservation for locally advanced rectal cancer (LARC). Combining immunotherapy with radiotherapy and chemotherapy has shown synergistic effects. This study a evaluates the efficacy and safety of long-term nCRT with camrelizumab (a PD-1 inhibitor) for LARC and low rectal cancer requiring anal preservation. Methods: In this single-arm, prospective, phase II trial, patients with newly diagnosed LARC (cT3-4N0M0 or cT1-4N+M0) and low rectal cancer requiring sphincter preservation (cT2N0M0, <5 cm from anal verge) were enrolled. All patients received long-course radiotherapy (50Gy/45Gy/25f) with concurrent chemotherapy [T2-3N0M0: capecitabine (1650 mg/m ² /d, bid, d1-14, Q3W); T4N0M0 or T1-4N+M0: capecitabine + oxaliplatin (130 mg/m ² , d1, Q3W)], plus camrelizumab (200 mg, d1, Q3W) for 4 cycles. Researchers evaluated patients after neoadjuvant therapy, followed by surgical resection. The primary endpoint was pathological complete response rate (pCR), and secondary endpoints included clinical complete response rate (cCR), objective response rate (ORR), disease control rate (DCR), disease-free survival, overall survival and safety. Results: Between January 2024 and December 2025, 58 patients were enrolled with 56 completing the efficacy evaluation. Among them, 2 patients achieved cCR, 22 patients had partial response, and 32 stable disease. The ORR was 42.9%, and DCR was 100%. Of 58 patients, 43 underwent surgery, 4 adopted wait and watch strategy (2 achieved cCR and 2 achieved near-cCR), 7 continued observation without surgery, 2 declined surgery, and 2 were in going therapy. All surgical patients achieved R0 resection, with pCR rate at 46.5% (20/43). Among the16 patients with low rectal cancer, 11 (68.8%) achieved anal sphincter preservation. In tumor regression grade (Mandard five-grade standard), 20 patients were Grade 1, 16 with Grade 2, 5 with Grade 3, and 2 with Grade 4. Regarding safety, 56 patients (100%) experienced treatment-related adverse effects, including lymphopenia (89.3%), reactive capillary endothelial proliferation (67.9%), leukopenia (39.3%), thrombocytopenia (33.9%), diarrhea (21.4%), fatigue (14.3%), and nausea (8.9%). Four patients reported Grade 3 adverse effects, predominantly lymphopenia (3.6%) and thrombocytopenia (3.6%). Patients generally tolerated treatment well, with symptoms managed and relieved symptomatically. Conclusions: Long-term neoadjuvant chemoradiotherapy (nCRT) with camrelizumab has shown promising rates of pathological complete response and clinical safety in patients with locally advanced and low rectal cancer aiming to preserve anal function. This ongoing study anticipates final results that may further enhance survival outcomes for these patients. Clinical trial information: NCT06304545 .