FDA Accepts sBLA for Pembrolizumab/Chemo in Gastric or GEJ Adenocarcinoma

The FDA has accepted a supplemental biologics license application for pembrolizumab (Keytruda) in combination with chemotherapy as a first-line treatment for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to a press release from Merck.¹

In the phase 3 KEYNOTE-859 trial, pembrolizumab plus chemotherapy improved OS compared with chemotherapy alone in patients with gastric or GEJ adenocarcinoma.

The FDA has set a Prescription Drug User Fee Act date of December 16, 2023 for this indication.

Supporting data for this application come from come from the phase 3 KEYNOTE-859 trial (NCT03675737), in which the addition of pembrolizumab to chemotherapy yielded a statistically significantly improved overall survival (OS) regardless of PD-L1 expression in patients with HER2-negative disease.

According to findings presented at the European Society for Medical Oncology Congress (ESMO) virtual plenary session in February 2023, the median OS was 12.9 months (95% CI, 11.9-14.0) with pembrolizumab plus chemotherapy vs 11.5 months (95% CI, 10.6-12.1) with placebo plus chemotherapy (HR, 0.78; 95% CI, 0.70-0.87; P <.0001).² Additionally, the 12-month OS rates were 52.7% and 46.7%, and the 24-month OS rates were 28.2% and 18.9% in each respective arm.

“We are committed to working closely with the FDA to bring [pembrolizumab] to more patients with gastric and [GEJ] cancer who are in need of additional treatment options that may help them live longer,” Scot Ebbinghaus, MD, vice president of global clinical development at Merck Research Laboratories, said in the press release.

Investigators of the double-blind, randomized phase 3 KEYNOTE-859 trial assessed pembrolizumab plus chemotherapy compared with placebo plus chemotherapy in a population of 1579 patients with gastric or GEJ adenocarcinoma.

Patients were randomly assigned to receive either 200 mg of pembrolizumab intravenously on day 1 of each 21-day cycle or matched placebo followed by a chemotherapy regimen consisting of cisplatin plus 5-fluoracil or oxaliplatin plus capecitabine.

The primary end point of the KEYNOTE-859 trial was OS. Secondary end points included progression-free survival, objective response rate, duration of response, adverse effects (AEs), and the percentage of patients discontinuing treatment due to AEs.

Patients 18 years and older who had histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma with known PD-L1 expression status were eligible for enrollment on the trial. Additional inclusion criteria included having HER2-negative disease, measurable disease based on RECIST v1.1 criteria, being able to provide a tumor tissue sample for PD-L1 and microsatellite instability biomarker analysis, having an ECOG performance status of 0 or 1, and adequate organ function.

Patients who had squamous cell or undifferentiated gastric cancer or preexisting peripheral neuropathy greater than grade 1 were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had previous therapy with an anti–PD-L1, anti–PD-1, or anti–PD-L2 agent; prior radiotherapy within 2 weeks prior to beginning study treatment; known active central nervous system metastases; or known hypersensitivity to pembrolizumab or any of its excipients.

The most common any-grade treatment-related AEs in the KEYNOTE-859 trial among patients receiving pembrolizumab vs the control arm included nausea (41.4% vs 41.4%), diarrhea (32.1% vs 27.2%), and anemia (31.0% vs 26.9%). Additionally, the most common any-grade immune-mediated AEs in each respective arm were hypothyroidism (15.3% vs 4.3%), hyperthyroidism (5.6% vs 1.7%), and colitis (3.3% vs 0.9%).

References

1. FDA accepts application for Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. News release. Merck. April 13, 2023. Accessed April 13, 2023. bit.ly/3UvYC9l
2. Rha SY, Wyrwicz LS, Yañez-Weber PE, et al. Pembrolizumab (pembro) plus chemotherapy (chemo) as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer: phase III KEYNOTE-859 study. Presented at ESMO Virtual Plenary; February 16-17, 2023. Accessed February 16, 2023.