Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study

Bo Long; Huinian Zhou; Zeyuan Yu; Junmin Zhu; Hanteng Yang; Zeping Huang; Dengwen Wei; Shigong Chen; Xiaojun Yang; Xiaoning Zhao; Wenjuan Zhang; Hong Yan; Xiaoying Guan; Long Li; Gengyuan Zhang; Hongwei Yu; Shengfu Che; Zhongti Gao; Xiangyan Jiang; Changjiang Luo; Jie Mao; Da Zhao; Yumin Li; Zebin Jiang; Zuoyi Jiao

doi:10.1016/j.medj.2024.10.008

Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study

Med. 2024 Nov 8:S2666-6340(24)00406-9. doi: 10.1016/j.medj.2024.10.008. Online ahead of print.

Authors

Bo Long¹, Huinian Zhou¹, Zeyuan Yu¹, Junmin Zhu¹, Hanteng Yang¹, Zeping Huang², Dengwen Wei³, Shigong Chen¹, Xiaojun Yang⁴, Xiaoning Zhao³, Wenjuan Zhang⁵, Hong Yan⁶, Xiaoying Guan⁶, Long Li¹, Gengyuan Zhang¹, Hongwei Yu¹, Shengfu Che¹, Zhongti Gao¹, Xiangyan Jiang¹, Changjiang Luo¹, Jie Mao¹, Da Zhao⁷, Yumin Li², Zebin Jiang⁴, Zuoyi Jiao⁸

Affiliations

¹ Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China.
² Lanzhou University Second Hospital, The Oncological Surgery Department, Lanzhou, China.
³ Sun Yat-sen University Cancer Center Gansu Provincial Cancer Hospital, The Gastrointestinal Surgery Department, Lanzhou, China.
⁴ Gansu Provincial Hospital, The General Surgery Department, Lanzhou, China.
⁵ Lanzhou University Second Hospital, The Radiology Department, Lanzhou, China.
⁶ Lanzhou University Second Hospital, The Pathology Department, Lanzhou, China.
⁷ The First Hospital of Lanzhou University, The Oncology Department, Lanzhou, China.
⁸ Lanzhou University Second Hospital, The General Surgery Department, Lanzhou, China; Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China. Electronic address: jiaozy@lzu.edu.cn.

PMID: 39536755
DOI: 10.1016/j.medj.2024.10.008

Abstract

Background: Treatment with cadonilimab and chemotherapy has shown promise as a first-line treatment for gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, its application in neoadjuvant settings has not yet been documented.

Methods: This multicenter, phase 2 trial (ChiCTR2200066893) was conducted at four hospitals across China. Treatment-naive patients with locally advanced G/GEJ adenocarcinoma (cT3/4, N+, M0) and who were human epidermal growth factor receptor 2 negative received 3-cycle or 4-cycle neoadjuvant treatment of cadonilimab plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, followed by gastrectomy and 4-cycle adjuvant FLOT chemotherapy. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR), overall response rate (ORR), disease control rate (DCR), R0 resection rate, downstaging rate, and safety.

Findings: Between December 23, 2022, and December 15, 2023, 32 of 38 patients completed the scheduled treatment, achieving an R0 resection rate of 100% (32/32). The pCR rate was 21.1% (8/38, 90% confidence interval [CI]: 9.7-32.4), and the MPR rate was 44.7% (17/38, 90% CI: 30.9-58.5). Radiological evaluations were available for 28 of 38 patients by blinded independent central review. The ORR was 60.7% (17/28, 90% CI: 44.7-76.7), and the DCR was 100.0% (28/28, 90% CI: 100.0-100.0). Tumor downstaging occurred in 71.9% of patients (23/32), with consistent efficacy across all populations observed in the subgroup analysis. Grade 3 adverse events occurred in 31.6% of patients without severe safety issues.

Conclusions: Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.

Funding: This study was funded by Akeso Biopharma.

Keywords: FLOT chemotherapy; Translation to patients; cadonilimab; dual anti-PD-1/CTLA-4 therapy; gastric/gastroesophageal junction adenocarcinoma; immunotherapy; neoadjuvant treatment.