This study is a randomized ,single center clinical study which is designed to investigate whether combination of Pembrolizumab with Lenvatinib could improve pCR rate and consequent survival in resectable mucosal melanoma. All the eligible patients were assigned to receive Lenvatinib once a day (QD) for 6 weeks plus pembrolizumab on Day 1 of each 21-day cycle (Q3W) concurrently on days 1 and 22, followed by surgery and 18 cycles of Pembrolizumab 200mg q3w of adjuvant phase.
Mucosal melanoma is a rare type of melanoma in Caucasian population and a dominate subtype in Asia, which generally carries a worse prognosis than cutaneous melanoma. Surgery remains the primary therapeutic intervention for mucosal melanoma, and neoadjuvant therapy is still needed which can lead to improvements in outcomes by surgical resectability, local control and organ preservation. Immunotherapy has showed promising activity in advanced melanoma. However, PD-1 antibodies, both Pembrolizumab and Nivolumab, showed much poorer response to mucosal melanoma than to cutaneous melanoma. Pembrolizumab showed modest objective response rate (ORR, 13%) in advanced mucosal melanoma in Chinese population (NCT02628067). Recent study also demonstrated that neoadjuvant therapy with one dose of Pembrolizumab could lead to pathological complete response (pCR) or major response in nearly 30% of resectable advanced melanoma and pCR was associated with reduced risk of recurrence and improved survival. Lenvatinib is also a kinase inhibitor that inhibits the kinase activities of VEGFR1,2, 3 which has been approved by FDA for differentiated thyroid cancer, advanced renal cell carcinoma and hepatocellular carcinoma. It is hypothesized that neoadjuvant Pembrolizumab in combination with Lenvatinib could result in higher anti-tumor activity with lower toxicity and prolong RFS and OS in high-risk resectable mucosal melanoma. The study will assess the efficacy and safety of the combination Pembrolizumab and Lenvatinib as neoadjuvant treatment in resectable mucosal melanoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
After enrollment, patients receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for 6 weeks; Lenvatinib 20mg orally once daily for 6 weeks. Patients conduct surgery within 1-4 weeks after the last dose of Pembrolizumab and Lenvatinib. After complete surgery, Pembrolizumab will be as adjuvant treatment for up to 15 cycles, 200mg IV on day 1 of every 21 day-cycles.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Pathological complete response (pCR) rate: defined as the percentage of subjects without alive tumor cells in the resected specimen post operation.
To evaluate pathological complete response (pCR) rate of Pembrolizumab combined with Lenvatinib as neoadjuvant therapy for resectable mucosal melanoma.
Time frame: Approximately 10 weeks
1 year RFS (recurrence-free survival) rate per RECIST1.1 as Assessed by investigator
To evaluate1-year RFS rate of Pembrolizumab combined with Lenvatinib as neoadjuvant therapy for resectable mucosal melanoma.
Time frame: Approximately 1 year
Overall survival
OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.
Time frame: Approximately 2 years
Incidence of AEs/SAEs
Adverse events (AEs) ; serious adverse events (SAEs); abnormal value of Lab test according to NCI-CTCAE V5.0
Time frame: Approximately 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Enrollment
26