FDA Grants Priority Review for Pembrolizumab in Progressive Cervical Cancer

The FDA has accepted a priority review for a new supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda; Merck) combined with external beam radiotherapy (EBRT), concurrent chemotherapy, and brachytherapy. This treatment is aimed to aid individuals that were newly diagnosed with high risk locally advanced cervical cancer.

Pembrolizumab is an anti-PD-1 therapy, supported by data from the phase 3 KEYNOTE-A18 trial (ENGOT-cx11/GOG-3047). The press release noted that this trial focused on the use of pembrolizumab combined with concurrent chemoradiotherapy, with primary endpoints of progression-free survival and overall survival.

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“The standard of care for patients with locally advanced cervical cancer has not changed in more than 2 decades, and the majority of patients will experience recurrence or progression of their disease,” said Gursel Aktan PhD, vice president, global clinical development, Merck Research Laboratories, in a press release. “If approved, Keytruda 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 Keytruda to these patients who are in need of additional treatment options.”

The trial enrolled 1060 patients who were randomized to receive either pembrolizumab or placebo. Participants had newly diagnosed high-risk locally advanced cervical cancer and were to receive treatment with definitive intent.

Pembrolizumab is a humanized monoclonal antibody and an anti-programmed death receptor-1 (PD-1) therapy, according to the press release. Its role is to increase the ability of the body’s immune system to recognize and fight tumor cells by blocking the interaction of the PD-1 with PD-L1 and PD-L2 to trigger T lymphocytes.

The indicated use of the pembrolizumab with chemotherapy or with bevacizumab is for individuals with persistent, recurrent, or metastatic cervical cancer with a PD-L1 tumor. However, pembrolizumab on its own has the same use, but during or after the tumors were treated with chemotherapy.

Because pembrolizumab blocks the PD-1 and PD-L1 pathways it creates a resistance of the immune response and could cause fatal immune response reactions. The press release noted that these immune-mediated adverse reactions include pneumonitis, colitis, hepatoxicity and hepatitis, endocrinopathies, renal dysfunction, and dermatologic adverse reactions. Other forms of pembrolizumab were discontinued in the past due to extensive adverse reactions.

Pembrolizumab is also reported to cause fatal infusion-reactions that include hypertensives and anaphylaxis. Patients should be monitored for symptoms of these reactions.

Reference

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. Merck. News release. September 20, 2023. Accessed September 20, 2023. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-concurrent-chemoradiotherapy-as-treatment-for-patients-with-newly-diagnosed-high-risk-locally-advanced/.