Treatment with Beigene‘s experimental therapy tislelizumab and chemotherapy resulted in durable responses and was overall well-tolerated in Chinese people with gastric/gastroesophageal junction (G/GEJ) adenocarcinoma or esophageal squamous cell carcinoma (ESCC), preliminary results of a Phase 2 trial show.
Researchers presented the results at the European Society for Medical Oncology Asia 2019 Congress, in Singapore, in a poster titled “Tislelizumab in combination with chemotherapy for Chinese patients (Pts) with gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal squamous cell carcinoma (ESCC).”
Tislelizumab is a type of immunotherapy known as immune checkpoint inhibitors. It binds to PD-1, a receptor expressed at the surface of immune cells that is sometimes hijacked by cancer cells to reduce immune surveillance. PD-1 inhibitors act by reactivating the immune response against the tumor.
Tislelizumab is different from other PD-1 antibodies because it has an engineered region that minimizes its interaction with other immune cells, which is thought to reduce adverse events.
The investigational therapy is being assessed in different types of cancers, including lung, liver, gastric, esophageal, and bladder cancers, as well as lymphoma.
The open-label, multi-center Phase 2 trial (NCT03469557) is assessing the effects of tislelizumab in combination with standard chemotherapy in people with G/GEJ adenocarcinoma or ESCC who have not received any previous treatments. Participants must have either locally advanced disease that’s unfit for surgical removal or metastatic cancer.
So far, 30 participants have been dosed, 15 with G/GEJ adenocarcinoma and 15 with ESCC. Eight participants — four of each cancer type — were still receiving treatment as of March 2019.
Seven patients (46.7%) in each group responded partially to the combination. The median response duration in the ESCC group was 12.8 months. The C/GEJ group had not reached this value yet, meaning that responses were ongoing in more than half of responders.
The median progression-free survival — time until signs of disease worsening or death — was 6.1 months in the G/GEJ adenocarcinoma group, and 10.4 months in the ESCC group.
After a median follow-up of 15.4 months in the G/GEJ adenocarcinoma group and 13.0 months in the ESCC group, median overall survival had not been reached in any group.
Overall, 85% of participants with ESCC were alive six months after the start of treatment, and 62% were alive after a year. The values for participants with G/GEJ adenocarcinoma were 71% after six months and 50% after a year.
The combination was generally well-tolerated in both groups. The adverse events reported were consistent with those of other PD-1 inhibitors in combination with chemotherapy.
All patients presented treatment-related adverse events, most of which were mild or moderate. The most common were low red blood cell count (anemia), decreased appetite, nausea, weakness, low white blood cell count, vomiting, low neutrophil count, and low platelet count.
Serious adverse events, such as increased blood bilirubin, difficulty swallowing, and fatigue, occurred in 13 participants, five with G/GEJ adenocarcinoma, and eight with ESCC.
One ESCC patient died of liver failure that was possibly related to the treatment.
“In this trial, the combination treatment of tislelizumab and chemotherapy demonstrated durable responses and was generally well-tolerated in patients with G/GEJ adenocarcinoma or ESCC,” Yong (Ben) Ben, MD, chief medical officer of immuno-oncology at BeiGene, said in a press release.
“Gastric cancer and esophageal cancer are among the most common cancer types worldwide, representing a high unmet need, particularly in China. We are excited to continue the late-stage development of tislelizumab in these and other highly prevalent cancers in Asia,” he said.