3106 - A Single Arm Phase II Study of Neoadjuvant Chemoradiotherapy and AK104 in pMMR/MSS Locally Advanced Rectal Cancer with Positive PD-L1 Expression

W. Xiao^1,2, R. Sun^1,2, H. Luo^1,2, Y. Wang^1,2, C. Zhu^2,3, P. Cai^2,4, X. Zhou^1,2, C. Li^2,5, R. X. Zhang^2,5, X. Wu⁵, L. Li^2,5, and G. Chen^2,5; ¹Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, ²State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China, ³Department of pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, ⁴Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, ⁵Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

Purpose/Objective(s): More recent data suggested that the combination of immune checkpoint inhibitors (ICIs) with chemoradiotherapy is efficacious against rectal cancer with proficient mismatch repair (pMMR), especially in patients with high programmed cell death 1 ligand 1 (PD-L1) expression. AK104 monotherapy, a humanized IgG1 bispecific antibody that simultaneously binds to programmed cell death protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), has shown promising efficacy and tolerable toxicity in multiple cancer types. The objective of this trial is to report the efficacy and safety of AK104 combined with long-course chemoradiotherapy for local advanced rectal cancer (LARC) with positive PD-L1 expression. The trial (clinicalTrials.gov, NCT05980689), a prospective, open label, single-arm phase II study, is underway. Materials/

Methods: Main inclusion criteria include: cT3-4aNany or cTanyN+ rectal adenocarcinoma aged 18-75years; MicroSatellite stability (MSS) and pMMR; positive PD-L1 expression (Tumor cell Proportion Score (TPS) = 1% or Combined Positive Score (CPS) =1); ECOG performance 0-1; distance = 12cm from anal verge. 33 patients will be enrolled in the trial. Patients will receive 2 cycles of neoadjuvant immunotherapy (AK104) during long-course radiotherapy (50Gy/25 fractions) and concurrent capecitabine, followed by another 3 cycles of AK104, finally received total mesorectal excision (TME) (or other treatment decisions, such as watch and wait) and adjuvant chemotherapy. Primary endpoint is the rate of complete response, including pathologic complete response (pCR) and clinical complete response (cCR). Secondary endpoints include rate of major pathologic response and tumor regression grade distribution, acute toxicity, surgical complications, long-term anal function, late toxicity, disease-free survival, and overall survival.
Results: The study has now enrolled three patients, and the study is still ongoing.
Conclusion: The study is ongoing.