Sintilimab plus oxaliplatin/capecitabine significantly improved overall survival over chemotherapy alone when used as a first-line treatment in patients with unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Sintilimab (Tyvyt) plus oxaliplatin/capecitabine significantly improved overall survival (OS) over chemotherapy alone when used as a first-line treatment in patients with unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, meeting the predefined primary end point of the phase 3 ORIENT-16 trial (NCT03745170).1
At an interim analysis, the OS benefit of sintilimab plus chemotherapy was noted in both the intention-to-treat population and a subset of patients with PD-L1 positivity.
Moreover, the toxicity profile of sintilimab proved to be consistent with what has previously been reported with the agent, with no new signals observed for the combination.
The data from the trial will be presented at an upcoming medical conference, according to Innovent Biologics, Inc., the drug developer. Moreover, the biopharmaceutical company shared plans to review these data and file a supplemental new drug application for the agent with the Drug Evaluation Center of the National Medical Products Administration in China based on a recommendation issued by the study’s Independent Data Monitoring Committee.
“ORIENT-16 is the first phase 3 clinical trial in China to demonstrate an anti–PD-1 antibody in combination with chemotherapy significantly prolonged OS in the first-line treatment of advanced gastric cancer,” Professor Jianming Xu, of the Fifth Medical Center of People’s Liberation Army General Hospital, stated in a press release. “Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China. The prognosis of advanced gastric cancer is very poor…The results of the ORIENT-16 study have the potential to bring a new and more effective treatment option to people with gastric cancer.”
Sintilimab is an immunoglobulin G4 monoclonal antibody that was designed to bind to PD-1 molecules on the surface of T cells, block the PD-1/PD-L1 pathway, and reactivate T cells to eliminate tumor cells.
The double-blind, multicenter phase 3 ORIENT-16 trial enrolled patients with a histologically confirmed diagnosis of unresectable locally advanced, recurrent, or metastatic gastric or GEJ adenocarcinoma, who were between the ages of 18 years and 75 years, had an ECOG performance status of 0 or 1, and had measurable disease per RECIST v1.1 criteria and investigator assessment.2
Patients also needed to have acceptable organ function, an expected survival of at least 12 weeks, and they could not have previously received neoadjuvant or adjuvant treatment with chemotherapy, radiotherapy, or both for their disease within the past 6 months.
If patients had suspicious active bleeding or obstruction phenomenon, HER2 positivity, a liver metastasis lesion that is 50% or bigger, grade 2 or higher peripheral sensory neuropathy, known DPD enzyme deficiency status, of if they previously received treatment with cisplatin at a dose of 300 mg/m2 or higher; a PD-L1, PD-L2, anti-CD137, anti–CTLA-4, or co-inhibitory T-cell receptor; or systemic treatment with corticosteroids, they were excluded.
Study participants on the investigative arm were administered sintilimab at a dose of 3 mg/kg every 3 weeks if they weighed under 60 kg, or 200 mg every 3 weeks if they weighed 60 kg or more. The novel agent was given on day 1 via intravenous (IV) infusion. Patients also received IV oxaliplatin at a dose of 130 mg/m2 every 3 weeks on day 1 plus IV capecitabine at a twice-daily dose of 1000 mg/m2 according to Body Surface Area every 3 weeks on days 1 through 14. Those in the control arm received the same dose and schedule of oxaliplatin plus capecitabine with placebo instead of sintilimab.
The primary end point of the trial was OS in all randomized patients and in the subset of patients with PD-L1–positive disease. Secondary end points include progression-free survival, duration of response, objective response rate, disease control rate, and safety.
“While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet in gastric cancer. The treatment options for advanced gastric cancer are very limited and the ORIENT-16 study aimed to help address this unmet medical need,” Zhou Hui, MD, senior vice president of Clinical Development at Innovent, stated in a press release. “These results are very encouraging and confirmed the clinical value of sintilimab plus chemotherapy in the first-line treatment of advanced gastric cancer. We are grateful for all contributions made by every investigator and patient in this study, and we hope that sintilimab can become a treatment option for people with gastric cancer.”