Abstract 493TiP
Background
The most common first-line treatment for advanced esophageal squamous-cell cancer (ESCC) is cisplatin-based chemotherapy combined with anti-PD1 antibody. The combination therapy including cisplatin presents clinical problems, such as a higher incidence of nausea or vomiting, renal toxicity, and requirement of frequent inpatient treatment. Oxaliplatin-based chemotherapy, such as modified-FOLFOX6 (mFOLFOX6), may offer a promising solution to these clinical issues. In addition, recent studies have shown that anti-PD1 antibody might exhibit synergistic effects with oxaliplatin through immunogenic cell death across various cancer types. However, the clinical data of oxaliplatin-based chemotherapy combined with anti-PD1 antibody is limited in patients with ESCC. We therefore planned a prospective trial to investigate the efficacy and safety of mFOLFOX6 plus nivolumab as initial therapy for advanced ESCC.
Trial design
This trial is a single-arm, multicenter, phase 2 study conducted at 8 institutes in Japan. Key inclusion criteria are patients with previously untreated, unresectable, recurrent, or metastatic ESCC (regardless of PD-L1 status), aged 18 years or older, ECOG PS of 0–2, measurable disease by RECIST ver1.1, and adequate organ function (creatinine clearance ≥ 30mL/min). Enrolled patients receive mFOLFOX6 (oxaliplatin 85 mg/m2, l-LV 200 mg/m2, and bolus 5-FU 400 mg/m2 on the first day, followed by continuous 5-FU 2,400 mg/m2 in 46 hours) plus nivolumab 240 mg/body every 2 weeks. Primary endpoint is objective response rate (ORR) per RESIST ver1.1 as assessed by the investigator. The threshold ORR and expected ORR are set to 24% and 47%, respectively. Based on an exact (upper-tailed) test of a binomial proportion with a one-sided 5% type I error and 80% statistical power, 33 patients will be enrolled, considering a 10% dropout rate. Secondary endpoints include overall survival, progression-free survival, disease control rate, duration of response and adverse events. This is the first trial to assess the clinical benefit and utility of mFOLFOX6 plus nivolumab for patients with ESCC. Patient enrollment began in February 2024.
Clinical trial identification
Japan Registry of Clinical Trials (jRCTs) No.031230630 (released on 2 Feb 2024).
Legal entity responsible for the study
St. Marianna University School of Medicine.
Funding
Japan Research Foundation for Clinical Pharmacology (JRFCP).
Disclosure
Y. Amanuma: Financial Interests, Institutional, Sponsor/Funding, corporate-sponsored research: Ono Pharmaceutical, Bristol Myers Squibb. M. Furuta: Financial Interests, Personal, Invited Speaker: Eli Lilly, Bristol Myers Squibb, Merck & Co., Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. T. Tsushima: Financial Interests, Personal, Invited Speaker: Taiho Pharma, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Taiho Pharma, MSD, Ono Pharmaceutical. T. Moriwaki: Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical, Bristol Myers, Yakult Honsha. Y. Sunakawa: Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., MSD K.K., Novartis Pharmaceuticals, Astellas Pharma Inc., Sysmex, Guardant Health; Financial Interests, Personal, Advisory Board: Merck Biopharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Guardant Health. All other authors have declared no conflicts of interest.