New drug for gastric patients significantly reduced the risk of death in patients with relapsed/refractory advanced gastric cancer.The ONO-4538-12 study, conducted by Japanese partner Ono Pharmaceutical (TYO: 4528), demonstrated that new drug 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.ONO-4538-12 is a Phase III, randomized, double-blind, placebo-controlled clinical trial evaluating new drug efficacy and safety in such patients.
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 new drug 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 new drug 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 new drug 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 new drug was consistent with previously reported studies in solid tumors. 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 new drug-treated and placebo-treated patients, respectively. The Grade 3/4 TRAEs reported in more than 2% of patients were diarrhea, fatigue, decreased appetite, pyrexia, as well as increased AST and ALT in the new drug group, and fatigue and decreased appetite in the placebo group.
“ONO-4538-12 is the first randomized, Phase III immuno-oncology trial to demonstrate improved survival for patients with previously treated advanced or recurrent gastric cancer. We find these results with new drug 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 Waxman, development lead, gastrointestinal oncology, at Bristol-Myers Squibb.“These results show a clinical benefit with new drug for patients with pre-treated advanced or recurrent gastric cancer and establish a strong basis for conducting additional studies with new drug as a treatment for patients with gastric cancer,” added lead study investigator Yoon-Koo Kang, of the Department of Oncology at the University of Ulsan College of Medicine, Asan Medical Center in Seoul, South Korea.