FDA Grants Priority Review to Pembrolizumab for Stage IIB or IIC Melanoma

The FDA has accepted and granted priority review to a biologics license application for pembrolizumab for the adjuvant treatment of adult and pediatric patients with stage IIB or IIC melanoma following complete resection.

The FDA has accepted and granted priority review to a biologics license application (BLA) for pembrolizumab (Keytruda) for the adjuvant treatment of adult and pediatric patients aged 12 years and older with stage IIB or IIC melanoma following complete resection, announced Merck, in a press release.

The decision for speedy review of the BLA follows news that patients with surgically resected high-risk stage II melanoma showed improvement in recurrence-free survival (RFS) on treatment with pembrolizumab compared with those treated with placebo in the phase 3 KEYNOTE-716 clinical trial (NCT03553836), meeting the primary end point of the trial. The target action date for the FDA’s decision has been set for December 4, 2021.

“KEYNOTE-716 is the first phase 3 study to evaluate adjuvant therapy solely for stage IIB and IIC melanoma–an area with high unmet need,” said Jason Luke, MD director, Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, in the release. “By moving immunotherapy with Keytruda to earlier stages of melanoma, we have the opportunity to reduce the risk of recurrence for high-risk stage II patients compared to observation alone following complete resection.”

KEYNOTE-716 is a randomized, double-blind study evaluating pembrolizumab administered at 2 mg/kg every 3 weeks for up to 17 cycles or matching placebo in approximately 954 patients with resected high-risk stage II melanoma in part 1. for pediatric patients and 200 mf for adult patients. Part 2 of the study allows patients in the pembrolizumab arm to received up to 35 cycles of the drug, including those who recurred after the first 17 cycles, but patients could not have experienced disease recurrence within 6 months. As secondary end points, the study is exploring distant metastasis-free survival, overall survival, the incidence of adverse events (AEs), and the incidence of discontinuations.

To be eligible for inclusion in KEYNOTE-716, patients were required to have surgically resected and histologically/pathologically confirmed new diagnosis of stage IIB or stage IIC cutaneous melanoma, be naïve to treatment beyond surgical resection 12 weeks prior to study entry, show no evidence of metastatic disease, and have an ECOG performance score of 0 or 1 or a Karnofsky performance score of ≥50 if between the ages of 16 and 18 years old. Patients must have also recovered well from any toxicity or complications related to surgery, and women could not be pregnant or breastfeeding, and must have been using contraception.

“At Merck, we are innovating to fight cancer earlier, and our data continues to build in this important area of research,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in the press release. “Many patients with stage II melanoma have a high risk of their cancer returning after surgery. This is an important milestone for patients, and we look forward to sharing these results with the medical community as soon as possible. We thank the patients and investigators for their participation in this study.”

Pembrolizumab is an anti-PD-1 therapy which already has indications in melanoma, non–small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high or mismatch repair deficient colorecta cancer, esophageal cancer, cervical cancer, and multiple other malignancies.

Safety data from multiple studies of pembrolizumab show that use of the agent can lead to immune-mediated pneumonitis in approximately 3.4% of patients, as well as immune-mediated colitis in roughly 1.7%, and hepatotoxicity and immune-mediated hepatitis in about 0.7% each.

Further, in a prior study that included patients with head and neck squamous cell carcinoma (KEYNOTE-012; NCT01848834), AEs were reported in17% of patients and serious AEs were seen in 45%. The most frequent AEs observed in the patients included fatigue, decreased appetite, and dyspnea. The most frequent serious AEs observed were pneumonia, dyspnea, confusion, vomiting, pleural effusion, and respiratory failure. These findings were considered to be similar to the melanoma population who received pembrolizumab.


Merck’s Keytruda® (pembrolizumab) significantly prolonged recurrence-free survival (RFS) compared to placebo as adjuvant therapy for patients with stage ii resected high-risk melanoma in phase 3 KEYNOTE-716 trial. News release. August 5, 2021. Accessed August 5, 2021. https://bit.ly/37jGpDV