CHICAGO—Investigators are now enrolling patients for a phase III trial, KEYNOTE-716, to assess the efficacy and safety of adjuvant pembrolizumab in adult and pediatric patients with surgically resected high-risk stage II melanoma. The study design was presented (abstract TPS9596) during a poster session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
“Patients with localized stage I/II melanoma are typically treated surgically. However, disease recurrence after surgery is common, and adjuvant treatment options that can safely lower the risk for distant recurrence in patients with stage II melanoma are lacking,” wrote the authors led by Matteo S. Carlino, BMedSc, MBBS, of the Melanoma Institute Australia at the University of Sydney.
In the KEYNOTE-054 trial, the immunotherapy pembrolizumab as adjuvant therapy has yielded significantly longer recurrence-free survival compared with placebo in patients with stage III melanoma (75.4% vs 61.0%, respectively). Based upon these promising results, the investigators initiated KEYNOTE-716, a two-part (adjuvant and rechallenge/crossover), randomized, double-blind, placebo-controlled, phase III study. Patients are currently being enrolled in Australia, Belgium, Brazil, Canada, Chile, France, Israel, Poland, Spain, Switzerland, the United Kingdom, and the United States.
Eligible patients are ≥ 12 years of age with newly diagnosed, completely resected stage IIB/IIC cutaneous melanoma. Exclusion criteria include mucosal, ocular, or uveal melanoma or prior treatment for melanoma (except for resection of the primary disease) within 12 weeks of initiating the study treatment. The investigators are seeking approximately 954 patients. The primary endpoint is recurrence-free survival. The secondary endpoints are distant metastasis–free survival, overall survival, and safety and tolerability.
In the first (blinded) part of the study, patients will be randomized to receive pembrolizumab (200 mg for patients ≥ 18 years or 2 mg/kg for patients ≥ 12 years to < 18 years with a maximum dose of 200 mg) or placebo every 3 weeks for 17 cycles. Blood and tumor tissue will be collected for assessment of biomarker expression, and stool samples will be collected for microbiome biomarker analysis.
The study treatment will begin no more than 12 weeks after complete resection. During treatment, tumor imaging will be performed every 24 weeks; after treatment, it will be performed every 6 months for the first 3 years and then yearly (for up to 2 years) or until recurrence. Safety will be assessed in all patients who receive at least one treatment. Adverse events will be recorded for 30 additional days after the end of treatment and 90 days for serious adverse events.
In the second (unblinded) phase, patients with confirmed recurrence who had received pembrolizumab will be rechallenged with pembrolizumab as in the first part of the study; patients who had received placebo will be crossed over to pembrolizumab. An additional 17 or 35 cycles of treatment will be given for resected recurrence (local or distant), respectively. Tumor imaging will be performed every 12 weeks during additional treatment.