EU’s CHMP Recommends Pembrolizumab Combo Approval in HER2+ Gastric Cancer

The FDA granted accelerated approval to pembrolizumab plus trastuzumab and chemotherapy for managing HER2-positive gastric or GEJ adenocarcinoma in May 2021.

The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has recommended approving pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and chemotherapy as a frontline treatment for patients with PD-L1–positive, HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to a press release form Merck.¹

Interim data from the phase 3 KEYNOTE-811 trial (NCT03615326) support the CHMP’s recommendation to approve this regimen. In the study, the addition of pembrolizumab significantly improved progression-free survival (PFS) and objective response rate (ORR) vs trastuzumab plus chemotherapy alone across a population in which more than 80% of patients had PD-L1–positive tumors. According to previously published findings, there was also a trend towards improved overall survival (OS) in the pembrolizumab arm that did not reach statistical significance.²

The European Commission will review the CHMP’s recommendation and decide on granting marketing authorization to this regimen in the European Union (EU) sometime in the third quarter of 2023.

“This positive CHMP opinion reinforces our commitment to bringing meaningful treatment options to patients living with HER2-positive gastric or GEJ cancer, whose tumors express PD-L1 with a combined positive score [of at least 1], in the [EU],” Scot Ebbinghaus, MD, vice president of global clinical development at Merck Research Laboratories, said in the press release. “We look forward to the European Commission’s decision and are excited at the possibility of bringing the first approved immunotherapy regimen for the first-line treatment of these patients with HER2-positive advanced gastric or GEJ cancer to the EU.”

Investigators of the randomized, double-blind phase 3 KEYNOTE-811 trial are assessing an estimated 732 patients with locally advanced, unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma across 2 treatment arms. Patients were randomly assigned to receive 200 mg of pembrolizumab or matched placebo every 3 weeks in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy.

The primary end points of the study are OS and PFS. Secondary end points include ORR, duration of response, and adverse effects.

Patients 18 years and older with histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma that is HER2 positive, as assessed by central review on the primary or metastatic tumor were eligible to enroll on the trial. Additional inclusion criteria included having measurable disease based on RECIST v1.1 criteria, a life expectancy of more than 6 months, adequate organ function, and an ECOG performance status of 0 or 1 within 3 days of study entry.

The FDA granted accelerated approval to pembrolizumab plus trastuzumab and chemotherapy for managing HER2-positive gastric or GEJ adenocarcinoma in May 2021.³ Supporting data for this approval came from the KEYNOTE-811 trial. Continued approval for this regimen is dependent on affirming its clinical benefits in confirmatory trials.

References

1. Merck receives positive EU CHMP opinion for KEYTRUDA® (pembrolizumab) plus trastuzumab and chemotherapy as first-line treatment for HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (CPS ≥1). News release. Merck. July 21, 2023. Accessed July 21, 2023. bit.ly/3XYbPcJ
2. KEYTRUDA® (pembrolizumab) plus trastuzumab and chemotherapy met primary endpoint of progression-free survival as first-line treatment in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. News release. June 16, 2023. Accessed July 21, 2023. bit.ly/3p903iB
3. FDA Approves Merck’s KEYTRUDA (pembrolizumab) combined with trastuzumab and chemotherapy as first-line treatment in locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma. News release. Merck. May 5, 2021. Accessed July 21, 2023. https://bit.ly/2SjmdOj