At present two studies (SWOG S1801 and NADINA) have demonstrated superiority when using neoadjuvant treatment compared to adjuvant treatment only, but no studies have compared PD-1 monotherapy (SWOG 1801 regimen) to the PD-1/CTLA-4 combination (NADINA regimen) therapy. The SWE-NEO study aims to compare these two regimens, where the PD-1/CTLA-4 combination is potentially more effective, but also associated with more side effects.
A phase III randomized controlled multicenter open-label trial. Patients will be randomized after a diagnosis of resectable stage III melanoma to have either two courses of CTLA-4 and PD-1 inhibitor combination therapy or PD-1 inhibitor monotherapy, before the pre-planned operation. In both arms, adjuvant treatment with a PD-1 inhibitor or with BRAF+MEK inhibitors in patients with a BRAF V600E mutation, will be given only to patients with no major pathological response in the operated tumor, with PD-1 inhibitor, or with BRAF+MEK inhibitors in patients with BRAF V600E mutation. Active follow-up will be performed for 3 years from surgery and followed for survival up until 10 years. Sequential blood and tumor samples will be collected for biomarker analyses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
128
Adjuvant monotherapy with Nivolumab
Adjuvant combination therapy with Nivolumab and Ipilimumab
Sahlgrenska University Hospital
Gothenburg, Sweden
RECRUITINGSkane University Hospital
Lund, Sweden
RECRUITINGKarolinska University Hospital
Stockholm, Sweden
RECRUITINGEvent-free survival (EFS)
Event-free survival (EFS), defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, or death from any cause (treatment-related, melanoma related or any other).
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Relapse-free survival (RFS)
Relapse-free survival (RFS), defined as time between date of surgery and date of melanoma recurrence, treatment-related death or melanoma-related death, whichever occurs first.
Time frame: From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Distant metastasis-free survival (DMFS)
Distant metastasis-free survival (DMFS), defined as time between date of randomization and date of first distant metastasis, treatment-related death or melanoma-related death, whichever occurs first.
Time frame: From date of randomization until the date of first documented distant metastasis or date of death from any cause, whichever came first, assessed up to 60 months
Overall survival (OS)
Overall survival (OS), defined as time between date of randomization and date of death.
Time frame: From date of randomization until the date of death from any cause, assessed up to 60 months
Major pathological response (MPR)
Major pathological response (MPR) (≤10% viable tumor cells), difference in MPR between combined ICI and monotherapy, central review of all surgical specimens by three expert melanoma pathologists.
Time frame: Start of neoadjuvant therapy to end of neoadjuvant therapy, up to approximately two months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Correlation of pathologic response to RFS, DMFS, and OS
Correlation of pathologic response in each arm to RFS, DMFS, and OS.
Time frame: From end of neoadjuvant therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Correlation of response to RFS, DMFS, and OS
Correlation of radiological and clinical response evaluation to RFS, DMFS, and OS.
Time frame: From end of neoadjuvant therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Proportion of patients having surgery according to plan
Number of patients having surgery according to plan (within 10 weeks from first neoadjuvant course).
Time frame: From start of neoadjuvant therapy to date of surgery, assessed up to 6 months
Surgical complication rates
Surgical complication rates according to Clavien-Dindo surgical classification.
Time frame: From surgery to date of any postoperative complication, assessed up to 3 months post surgery
Frequency of treatment-related adverse events (AEs)
Frequency of all grade and grade 3-5 treatment-related adverse events (AEs) according to CTCAE 5.0.
Time frame: From start of neoadjuvant therapy up to 1 year after last treatment