FDA Grants Accelerated Approval to Pembrolizumab/Trastuzumab Combination for HER2+ Gastric/GEJ Cancers

Based on response data from a randomized phase 3 trial, the FDA granted accelerated approval to pembrolizumab plus trastuzumab and chemotherapy for the treatment of HER2-positive gastric tumors.

The combination regimen of pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy was granted accelerated approval by the FDA for the treatment of patients with HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma that is locally advanced or metastatic.

The decision is supported by data from the phase 3 KEYNOTE-811 trial (NCT03615326), which examined trastuzumab plus chemotherapy and either pembrolizumab or placebo as therapy for patients with HER2-positive gastric cancer.

“Today’s approval marks an important milestone, as this is the first time an anti-PD-1 therapy has been approved in combination with anti-HER2 therapy and chemotherapy as a first-line treatment for these patients,” Dr. Roy Baynes, senior vice president and head of global clinical development and chief medical officer at Merck Research Laboratories, said in a press release. “From the start of Keytruda’s development, we have thoughtfully pursued novel combinations to help more patients with cancer. We are pleased to bring a new first-line combination regimen with KEYTRUDA that has shown meaningful improvement in ORR over standard treatment to patients with HER2-positive gastric and GEJ cancer.”

The multicenter, randomized, double-blind study assigned patients 1:1 to receive intravenous pembrolizumab at 200 mg or placebo added to trastuzumab at 8 kg/mg plus fluorouracil at 800 mg/m2 and either cisplatin at 80 mg/m2 or capecitabine at 1000 mg/m2.

The dual primary end points for the trial are progression-free survival and overall survival. The main efficacy data for this analysis were based on the objective response rate, which was significantly improved in the pembrolizumab arm at 74% (95% CI, 66%-82%) versus 52% (95% CI. 43%-61%) in the placebo arm (1-sided P <.0001). Corresponding complete response rates were 11% and 3.1%. These results were statistically significant. Median duration of response was 10.6 months (range, 1.1+ to 16.5+) with pembrolizumab versus 9.5 months (range, 1.4+ to 15.4+) with placebo.

The safety profile of pembrolizumab in this indication is similar to the known safety profile of the agent.

The trial is actively recruiting patients, with a total enrollment goal of 732 patients. Patients must have histologically or cytologically confirmed, previously untreated, locally advanced or metastatic HER2-positive GEJ adenocarcinoma, with HER2-positivity defined as immunohistochemistry 3+ or 2+ in combination with fluorescence in situ hybridization. Patients must have measurable disease per RECIST 1.1, an ECOG performance status of 0 or 1, a life expectancy greater than 6 months, and adequate organ function.


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 May 5, 2021. https://bit.ly/2SjmdOj