NEOSUMMIT-01 Trial: Perioperative Toripalimab for Locally Advanced Gastric Cancer

The results of the NEOSUMMIT-01 trial indicate that adding the PD-1 inhibitor toripalimab to perioperative chemotherapy significantly improves the pathological response in patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma.

According to the study published in Nature, patients receiving the combination therapy achieved a higher proportion of tumor regression grade (TRG) 0/1 compared to those receiving chemotherapy alone.

The primary endpoint of the trial was the pathological complete response or near-complete response rate, defined as TRG 0/1.

Trial Design and Methodology

NEOSUMMIT-01 was a randomized, open-label, phase 2 study involving patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN+M0.

The participants were randomized in a 1:1 ratio into two distinct treatment groups, with 54 patients assigned to each arm.

The chemotherapy group received three preoperative and five postoperative 3-week cycles of SOX/XELOX.

The toripalimab plus chemotherapy group received the PD-1 inhibitor toripalimab combined with SOX/XELOX, followed by toripalimab monotherapy for a period of up to six months.

Pathological Response Outcomes

The trial found that 44.4% of patients in the toripalimab plus chemotherapy group achieved TRG 0/1, compared to 20.4% in the chemotherapy-only group.

The risk difference for TRG 0/1 between the two groups was 22.7%, with a 95% confidence interval of 5.8% to 39.6% and a P-value of 0.009, meeting the prespecified endpoint.

the rate of pathological complete response (ypT0N0) was notably higher in the combination group at 22.2%, compared to 7.4% in the chemotherapy group, resulting in a P-value of 0.030.

Safety and Morbidity Data

The study also evaluated surgical morbidity and mortality to determine if the addition of toripalimab impacted surgical outcomes.

Surgical morbidity was reported at 11.8% for the toripalimab plus chemotherapy group, and 13.5% for the chemotherapy group.

Mortality rates were 1.9% in the combination group and 0% in the chemotherapy group.

Treatment-related grade 3–4 adverse events occurred in 35.2% of patients receiving toripalimab and chemotherapy, compared to 29.6% of patients in the chemotherapy-only arm.

The researchers concluded that the surgical morbidity, mortality, and treatment-related adverse events were comparable between the two treatment groups.