Merck’s press release announced positive data from the KEYNOTE-826 trial investigating pembrolizumab plus chemotherapy with or without bevacizumab for patients with cervical cancer.
The phase 3 KEYNOTE-826 trial (NCT03635567), which examined pembrolizumab (Keytruda) plus platinum-based chemotherapy, with or without bevacizumab (Avastin), met its dual primary end points in a population of patients with persistent, recurrent, or metastatic cervical cancer in the first-line setting, according to a press release from drug developer Merck.
The results of the study’s interim analysis highlighted that combination yielded statistically significant and clinically meaningful improvements in the dual primary end points of overall survival (OS) and progression-free survival (PFS).
“Despite progress with prevention and screening, cervical cancer continues to be a major health problem, often affecting younger and middle-aged women,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, said in a press release. “Women diagnosed with metastatic cervical cancer have a particularly poor prognosis, and there is an urgent need for new treatment options.”
The randomized, triple-blind, phase 3 trial enrolled adult patients with persistent, recurrent, or metastatic disease who did not previously receive systemic chemotherapy and were no longer candidates for curative treatments such as surgery and/or radiation.
A total of 617 patients were enrolled and randomized to receive either pembrolizumab 200 mg intravenously or placebo plus investigator’s choice of 1 of the platinum-based chemotherapy regimens on day 1 of each 21-day cycle for up to 35 cycles. The chemotherapy regimens included paclitaxel (175 mg/m2) plus cisplatin (50 mg/m2) with or without bevacizumab (15 mg/kg); or paclitaxel (175 mg/m2) plus carboplatin Area Under the Curve (AUC) 5 with or without bevacizumab (15 mg/kg). The control group was treated with placebo plus investigator's choice of platinum-based chemotherapy.
Secondary end points of the trial included objective response rate, duration of response, and safety.
The trial enrolled female patients who were aged 18 years or older with measurable disease per RECIST 1.1 criteria and could provide either archival tumor tissue or a newly obtained core biopsy or excisional biopsy.2 Patients were also required to have an ECOG performance status of 0-1 and have adequate organ function.
Patients with active central nervous system metastases were not able to enroll, with the exception of those whose metastases had been treated without the use of chemotherapy. Moreover, those who had an additional malignancy that was progressing or in need of treatment, an immunodeficiency or was receiving treatment with chronic systemic steroid therapy, or had an autoimmune disease requiring systemic treatment within the last 2 years were not eligible for enrollment.
Along with meeting the dual primary end points, the combination anti–PD-1 combination therapy produced a safety profile that was consistent with data previously reported in research with this agent.
The KEYNOTE-826 trial is a confirmatory study for the current accelerated approval for pembrolizumab in the second-line setting for patients with recurrent or metastatic cervical cancer and PD-L1–expressing tumors who have experienced disease progression on or after chemotherapy.
Findings from the trial are expected to read out at an upcoming medical conference and submitted to regulatory authorities.
“KEYNOTE-826 is the first study to show positive results for immunotherapy in first-line persistent, recurrent or metastatic cervical cancer, and we look forward to sharing these findings at an upcoming congress and discussing them with regulatory authorities,” explained Baynes in a press release. “We thank the patients, their caregivers and investigators for their participation in this important study.”
1. Merck announces phase 3 KEYNOTE-826 trial met dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent or metastatic cervical ancer. News release. Merck. Published June 22, 2021. Accessed June 22, 2021. https://bit.ly/3zI1iG5
2. Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826). ClinicalTrials.gov. Updated November 13, 2020. Accessed June 22, 2021. https://clinicaltrials.gov/ct2/show/NCT03635567