A phase Ib/II, multicenter, open-label study of AK104, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy (chemo) as first-line therapy for advanced gastric (G) or gastroesophageal junction (GEJ) cancer.
Jiafu Ji, Lin Shen, Xiangyu Gao, Ke Ji, Ye Chen, Nong Xu, Tianshu Liu, Nong Yang, Haijun Zhong, Ziyu Li, Changzheng Li, Zengqing Guo, Qingxia Fan, Xiaoyan Lin, Zhifang Yao, Wei Liu, Baiyong Li, Yu Xia
Abstract
308 Background: Anti-PD-1 agent plus chemo as first-line therapy for advanced G/GEJ cancer (Checkmate-649) yields OS and PFS benefits compared to chemo alone, indicating synergistic activity between immune checkpoint inhibitors and chemo. The combination of anti-PD-1 and anti-CTLA-4 has consistently demonstrated higher response rate compared to PD-1 monotherapy but higher toxicity. Here, we performed this phase Ib/II study to evaluate the efficacy and safety of AK104, a PD-1/CTLA-4 bispecific antibody, combined with XELOX (capecitabine combined with oxaliplatin) or modified XELOX (mXELOX) in the first-setting of G/GEJ cancer cohorts. This study is registered on ClinicalTrials.gov (NCT03852251). Methods: Pts with unresectable advanced G/GEJ adenocarcinoma and no prior systemic therapy, regardless of PD-L1 status were enrolled, excluding known HER2-positive pts. Enrolled patients received AK104 (4 mg/kg, 6 mg/kg, 10 mg/kg, Q2W or 10 mg/kg, 15mg/kg Q3W) + chemo (mXELOX Q2W or XELOX Q3W). The primary endpoint was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Results: As of 13 Aug 2021, 96 pts were enrolled with median age 62.7 years (range: 29–75), 70.8% male, 62.5% ECOG PS 1, 44.8% liver metastasis. The median follow-up was 9.95 months (range, 0.4-26.8). 88 patients (92%) had at least one post-baseline tumor evaluation. The ORR was 65.9% (58/88) with 2 (2.3%) complete responses and 56 (63.6%) partial responses. The disease control rate (DCR) was 92.0% (81/88). The median duration of response (DoR) was 6.93 months (95%CI, 4.60 to 11.20). The median PFS was 7.10 months (95%CI, 5.55 to 10.48). The median OS was 17.41 months (95%CI, 12.35 to NE). In pts with PD-L1 CPS≥1 vs CPS＜1, median OS was 17.41 months and 14.65 months, respectively. Treatment-related adverse events (TRAEs) occurred in 97.9% of pts, and the most frequent were platelet count decreased (60.4%), white blood cell count decreased (58.3%), neutrophil count decreased (56.3%), anaemia (47.9%), nausea (30.2%), vomiting (30.2%), aspartate aminotransferase increased (30.2%). Grade ≥3 TRAEs occurred in 62.5% pts. No new safety signals were identified. Conclusions: AK104 in combination with mXELOX/XELOX showed promising activity and manageable safety in previously untreated pts with advanced G/GEJ adenocarcinoma. AK104 + chemo represents a potential new first-line treatment option for these pts. A phase III study of AK104 combined with chemo as first-line therapy for G/GEJ cancer is underway. Clinical trial information: NCT03852251.