FDA Grants Priority Review to Pembrolizumab Plus Chemotherapy in Endometrial Cancer

The sBLA for pembrolizumab plus chemotherapy in endometrial cancer has been granted priority review by the FDA.

The FDA has granted priority review to the supplemental biologics license Application (sBLA) of pembrolizumab (Keytruda) plus standard-of-care chemotherapy, followed by pembrolizumab monotherapy for the treatment of patients with primary advanced or recurrent endometrial carcinoma. Notably, the Prescription Drug User Fee Act has been set for June 21, 2024, by the FDA.1

The sBLA is supported by findings from the phase 3 NRG-GY018 trial (NCT03914612), which were presented during the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and simultaneously published in the New England Journal of Medicine.2

“Endometrial cancer is the most common type of gynecological cancer, and front line treatment options are limited for patients with advanced stage or recurrent disease,” Ramez N. Eskander, a gynecologic oncologist and assistant professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of California San Diego, Moores Cancer Center, said in a press release.1 “The use of pembrolizumab in this setting has the potential to address a significant unmet need for these patients.”

NRG-GY018 was a double-blind, placebo-controlled study that randomly assigned patients 1:1 with stage III to IVB or recurrent endometrial cancer to receive pembrolizumab or placebo in combination with paclitaxel plus carboplatin. The study included a cohort of patients in both arms with mismatch repair-deficient (dMMR; n = 255) and mismatch repair-proficient (pMMR; n = 588) disease. The primary end point was progression-free survival (PFS); secondary end points included overall survival, safety, and health-related quality of life.

At a median follow-up of 12 months, patients in the dMMR cohort who received pembrolizumab (n = 112) did not reach (NR) a median PFS (NR; 95% CI, 30.6-NR) compared with a median PFS of 7.6 months (95% CI, 6.4-9.9) in the placebo arm (n = 113; HR, 0.30; 95% CI, 0.19-0.48; P < .001). Moreover, at a median follow-up of 7.9 months, patients in the pMMR cohort who received pembrolizumab (n = 290) achieved a median PFS of 13.1 months (95% CI, 10.5-18.8) compared with 8.7 months (95% CI, 8.4-10.7) among those who received placebo (n = 292; HR, 0.54; 95% CI, 0.41-0.71; P < .001).

Eligible patients received paclitaxel plus carboplatin in combination with either pembrolizumab or placebo for 6 cycles, followed by pembrolizumab or placebo maintenance therapy every 6 weeks for a maximum of 14 cycles; up to 20 total cycles of pembrolizumab or placebo were permitted. Intravenous (IV) pembrolizumab or placebo was administered at a dose of 200 mg every 3 weeks in combination with chemotherapy, then IV pembrolizumab or placebo was given at a dose of 300 mg every 6 weeks.

The baseline characteristics were well balanced between the dMMR and pMMR populations; the median age was 66 years (range, 37-85) compared with 65.5 years (range, 29-93), respectively. Most patients in both cohorts were White (79.1% vs 72.1%), had an ECOG performance status of 0 (64.4% vs 67.0%) and did not receive prior chemotherapy (94.2% vs 74.7%). 

In terms of safety, patients in the dMMR cohort experienced any-grade adverse effects (AEs) at a rate of 98.2% vs 99.1% in the pembrolizumab (n = 109) and placebo (n = 106) arms, respectively. In the pMMR cohort, these rates were 93.5% vs 93.4% in the pembrolizumab (n = 276) and placebo (n = 274) arms, respectively. Grade 3 or higher AEs occurred in the dMMR cohort at rates of 63.3% vs 47.2%, respectively, and at respective rates of 55.1% vs 45.3% in the pMMR cohort.

“If approved, pembrolizumab would be the first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status,” Gursel Aktan, PhD, vice president of global clinical development at Merck Research Laboratories, said in the press release. “We are committed to working closely with the FDA to bring pembrolizumab to these patients who are in need of additional treatment options, and we thank our collaborators for their partnership on this study.”

References

  1. FDA grants priority review to Merck’s application for KEYTRUDA® (pembrolizumab) plus chemotherapy as treatment for primary advanced or recurrent endometrial carcinoma. News release. February 20, 2024. Accessed February 20, 2024. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-chemotherapy-as-treatment-for-primary-advanced-or-recurrent-endometrial-carcinoma/
  2. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/NEJMoa2302312