Pembrolizumab Combo Receives FDA Priority Review in Cervical Cancer

The FDA set a Prescription Drug User Fee Act date of January 20, 2024 for the pembrolizumab-based regimen in newly diagnosed high-risk locally advanced cervical cancer.

The FDA has granted priority review to a supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) plus external beam radiotherapy (EBRT) and concurrent chemotherapy followed by brachytherapy as a treatment for patients with newly diagnosed high-risk, locally advanced, cervical cancer, according to a press release from Merck.¹

The regulatory agency set a Prescription Drug User Fee Act date of January 20, 2024 for the pembrolizumab-based regimen in this indication.

Supporting findings for the sBLA came from the phase 3 KEYNOTE-A18 trial (NCT04221945), in which investigators reported a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab plus concurrent chemoradiotherapy vs concurrent chemoradiotherapy on its own.² At the time of the prespecified interim analysis, investigators also observed a favorable overall survival (OS) trend in the pembrolizumab group, although these data were not considered to be mature.

Pembrolizumab’s safety profile in the KEYNOTE-A18 trial was comparable with previous reports of the agent, and investigators reported no new safety signals.

“The standard of care for patients with locally advanced cervical cancer has not changed in more than two decades, and the majority of patients will experience recurrence or progression of their disease,” Gursel Aktan, MD, PhD, vice president of Global Clinical Development at Merck Research Laboratories, said in the press release.¹ “If approved, [pembrolizumab] will be the first immunotherapy available for patients with newly diagnosed high-risk locally advanced cervical cancer. We are committed to working closely with the FDA to bring [pembrolizumab] to these patients who are in need of additional treatment options.”

In the experimental arm of the double-blind KEYNOTE A-18/ENGOT-cx11/GOG-3047 trial, patients received 200 mg of pembrolizumab intravenously once every 3 weeks for 5 cycles followed by 400 mg intravenously once every 6 weeks for 15 additional cycles plus 40 mg/m² of intravenous cisplatin once every week for 5 or 6 weeks. Patients then received EBRT followed by brachytherapy at a minimum total dose of 80 Gy for volume-directed and 75 Gy for point-directed treatment. Patients in the comparator arm received matched placebo plus concurrent chemoradiotherapy followed by EBRT and brachytherapy.

The trial’s primary end points were investigator-assessed PFS per RECIST v1.1 criteria and OS. Secondary end points included complete response rate, objective response rate, PFS, and OS in patients with PD-L1–positive disease, adverse effects, and quality of life.

Patients 18 years and older with high-risk locally advanced cervical cancer that is stage IB2 to IIB or stage III to IVA according to International Federation of Gynecology and Obstetrics (FIGO) 2014 criteria were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, available tissue sample from a core incisional or excisional biopsy of a tumor lesion, radiographically evaluable disease per RECIST v1.1 criteria, and adequate organ function within 7 days of beginning study treatment. Patients who received no prior definitive surgical, radiation, or systemic therapy for cervical cancer were also eligible for enrollment.

References

1. FDA grants priority review to Merck’s application for KEYTRUDA® (pembrolizumab) plus concurrent chemoradiotherapy as treatment for patients with newly diagnosed high-risk locally advanced cervical cancer. News release. Merck. September 20, 2023. Accessed September 20, 2023. https://shorturl.at/GMVZ4
2. Merck announces phase 3 KEYNOTE-A18 trial met primary endpoint of progression-free survival (PFS) in patients with newly diagnosed high-risk locally advanced cervical cancer. News release. Merck. July 19, 2023. Accessed September 20, 2023. https://shorturl.at/qxFR2