2266 - Hypofractionated Radiotherapy Combined with Nal-IRI + 5-FU/LV, Enlonstobart and Target Therapy in Locally Recurrent Rectal Cancer (NOVELTY-R): A Single-Arm Open-Label, Phase II Trial

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 19

POSTER

Presenter(s)

Ruiyan Wu, MD, PhD - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai,

R. Wu¹, J. Wan¹, L. Shen¹, F. Xia¹, H. Zhang¹, Y. Liu¹, Y. Wang¹, S. Zhou¹, X. Li², and Z. Zhang³; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, ³Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Shanghai Clinical Research Center for Radiation Oncology; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China

Purpose/Objective(s):

Pelvic recurrence occurs in 2.6% - 32% of rectal cancer patients following initial radical resection, and local recurrence rates can be as high as 20% after rectal cancer surgery. Consequently, locally recurrent rectal cancer (LRRC) remains a critical and challenging therapeutic focus. Hypofractionated radiotherapy holds promise for enhancing tumor sensitivity to immunotherapy. Short-course hypofractionated radiotherapy for the rectum may exhibit superior synergy with anti-PD-1/PD-L1 antibody compared to long-course conventionally fractionated radiotherapy. This study aims to evaluate the efficacy and safety of a combination regimen comprising hypofractionated radiotherapy, liposomal irinotecan plus 5-FU and leucovorin (nal-IRI + 5-FU/LV), anti-PD-1 therapy, and targeted therapy in patients with LRRC.

Materials/Methods:

Eligible patients were aged 18-75 years with LRRC and had not received any prior radiotherapy within 12 months. The inclusion LRRC patients were failed to oxaliplatin treatment in prior chemotherapy or chemoradiotherapy due to toxicity or progression. Patients received hypofractionated radiotherapy targeting both the locally recurrent site and oligometastatic lesions. This was combined with a chemotherapy regimen administered every two weeks (q2w), consisting of: 5-fluorouracil (2400 mg/m² via 48-hour continuous intravenous infusion), leucovorin (400 mg/m² IV), liposomal irinotecan (70 mg/m² IV), and Enlonstobart (240 mg IV). Targeted therapy with either bevacizumab (5 mg/kg IV on day 1) or cetuximab (with a loading dose of 400 mg/m² IV over >2 hours, followed by 250 mg/m² IV over 60 minutes weekly, or 500 mg/m² IV over >2 hours on day 1, q2w) was administered concurrently. Following this induction therapy, patients were reviewed by a multidisciplinary team (MDT) to determine subsequent management, which could include radical surgery or sustained systemic therapy with or without local treatment for unresectable disease.

Results:

As of January 7, 2026, 23 patients were enrolled with a median age of 57 years. Among the 12 efficacy-evaluable patients, the regimen yielded a complete response rate of 33.3% (4/12), an objective response rate (ORR) of 83.3% (10/12) and a disease control rate (DCR) of 91.7% (11/12). Grade =3 treatment-emergent adverse events (TEAEs) occurred in 8 of 23 patients (34.8%). The most common TEAEs were Lymphocyte count decreased (13.0%) and Diarrhoea(13.0%), followed by Neutrophil count decreased (8.7%). Vomiting, White blood cell count decreased, and Myelosuppression each occurred in 1 patient (4.3%).

Conclusion:

Hypofractionated radiotherapy combined with nal-IRI + 5-FU/LV, Enlonstobart and target therapy demonstrates promising anti-tumor activity and controllable safety in LRRC, and is worthy of further exploration.