The results of trial ONO-4538-12 were announced today, demonstrating nivolumab significantly reduced the risk of death by 37% (HR 0.63; p<0.0001) in patients with previously treated advanced gastric cancer refractory to or intolerant of standard therapy, a condition without current standard-of-care treatments.

The ONO-4538-12 data are being presented today in a late-breaking oral presentation at the 2017 Gastrointestinal Cancers Symposium in San Francisco, California.

ONO-4538-12 (NCT02267343) is a Phase 3, randomised, double-blind, placebo-controlled clinical trial conducted in Japan, Korea and Taiwan, evaluating the efficacy and safety of nivolumab in patients with unresectable (unable to be removed with surgery) previously treated advanced or recurrent gastric cancer, including gastroesophageal junction cancer, refractory to or intolerant of standard therapy.

Gastric cancer, also known as stomach cancer, is the fifth most common malignancy in the world, with more than 950,000 patients diagnosed each year, and is the third leading cause of cancer-related death, with more than 720,000 deaths reported annually.

The prevalence of gastric cancer is higher in East Asian countries than in Western countries.

While the five-year survival rate for people with gastric cancer is 30.4%, this rate falls to approximately 5% for those whose gastric cancer has metastasised (or spread).

Because no standard-of-care treatment options exist for patients with unresectable advanced or recurrent gastric cancer after chemotherapy, there remains an important unmet medical need for patients with this condition.

The primary endpoint of the study is overall survival (OS).

Median OS was 5.32 months (95% CI: 4.63 to 6.41) for patients treated with nivolumab, compared to 4.14 months (95% CI: 3.42 to 4.86) (p<0.0001) for those treated with placebo.

In addition, the 12-month OS in the nivolumab group was 26.6% (95% CI: 21.1 to 32.4) versus 10.9% (95% CI: 6.2 to 17.0) in the placebo group.

Patients treated with nivolumab also experienced an objective response rate of 11.2% (95% CI: 7.7 to 15.6) compared to 0% (95% CI: 0.0 to 2.8) with placebo and a median duration of response of 9.53 months (95% CI: 6.14 to 9.82), which were secondary endpoints.

The safety profile of nivolumab was consistent with previously reported studies in solid tumours.

Treatment-related adverse events (TRAEs) of any grade and Grade 3/4 occurred in 42.7% versus 26.7% and 10.3% versus 4.3% of nivolumab-treated and placebo-treated patients, respectively.

The Grade 3/4 TRAEs reported in more than 2% of patients were diarrhoea, fatigue, decreased appetite, pyrexia, as well as increased AST and ALT in the nivolumab group, and fatigue and decreased appetite in the placebo group.

The nivolumab and placebo-treated patients had similar rates of TRAEs leading to discontinuation, 2.7% and 2.5%, respectively.

“ONO-4538-12 is the first randomised, Phase 3 Immuno-Oncology trial to demonstrate improved survival for patients with previously treated advanced or recurrent gastric cancer. We find these results with nivolumab encouraging, as gastric cancer is a leading cause of cancer death globally and unmet needs remain for patients with advanced forms of this disease who become intolerant to chemotherapy or for whom such treatment has failed,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Oncology, Bristol-Myers Squibb, who produce nivolumab under the brand name Opdivo.

“These results show a clinical benefit with nivolumab for patients with pretreated advanced or recurrent gastric cancer and establish a strong basis for conducting additional studies with nivolumab as a treatment for patients with gastric cancer,” added lead study investigator Yoon-Koo Kang, M.D., Ph.D., of the Department of Oncology at the University of Ulsan College of Medicine, Asan Medical Center in Seoul, Korea.

This trial was conducted by Ono Pharmaceutical Co. Ltd. of Japan, Bristol-Myers Squibb’s development partner for nivolumab

Source: 2017 Gastrointestinal Cancers Symposium in San Francisco.