Phase 3 Trial Showed Pembrolizumab in Combination With Chemotherapy Had Statistically Significant Improvement in Overall Survival in HER2-Negative Gastric, Gastroesophageal Junction Adenocarcinoma

Positive topline results from the pivotal phase 3 KEYNOTE-859 trial (NCT03675737) investigating pembrolizumab (Keytruda, Merck) in combination with chemotherapy showed a statistically significant and clinically meaningful improvement in overall survival versus chemotherapy alone in an all-randomized patient population at a pre-specified interim analysis. An anti-programmed death receptor (anti-PD-1) therapy, pembrolizumab is used in combination with chemotherapy for the first-line treatment of patients with human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Additionally, the trial data demonstrated that pembrolizumab in combination with chemotherapy also had statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall response rate (ORR) as well. In the safety profile of pembrolizumab, the trial was shown to be consistent with what was observed in previously reported studies, with no new safety signals identified.

“Despite improvements in cancer care, advanced gastric cancer continues to have one of the lowest 5-year survival rates, and new interventions are urgently needed. The results from KEYNOTE-859 show the potential of KEYTRUDA plus chemotherapy to improve survival beyond chemotherapy alone for patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression,” said Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a press release.

Pembrolizumab works by increasing the ability of the body’s immune system to help detect and fight tumor cells. It is a humanized monoclonal antibody that inhibits the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which means activating T lymphocytes may affect both tumor cells and healthy cells.

The KEYNOTE-859 phase 3 trial evaluating pembrolizumab in combination with chemotherapy enrolled 1579 patients who were randomized to receive pembrolizumab at 200 mg every 3 weeks for up to approximately 2 years in combination with fluoropyrimidine- and platinum-containing chemotherapy, or placebo in combination with chemotherapy.

“We are excited by these new results that demonstrate our commitment to exploring new treatment options for patients fighting gastrointestinal cancers with KEYTRUDA and thank all investigators and patients who participated in this trial,” Barr said in the press release.

REFERENCE

Merck Announces Phase 3 KEYNOTE-859 Trial Met Primary Endpoint of Overall Survival in Patients With HER2-Negative Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. BusinessWire. November 22, 2022. Accessed November 23, 2022. https://www.businesswire.com/news/home/20221122005263/en