Neoadjuvant Ipilimumab Plus Nivolumab Versus Standard Adjuvant Nivolumab in Macroscopic Stage III Melanoma
Status:
Recruiting
Trial end date:
2027-01-01
Target enrollment:
Participant gender:
Summary
This is an international (Australia, Europe, and USA) open-label two-arm randomized phase 3
trial including 420 stage III (≤3 resectable in-transit metastases allowed) cutaneous or
unknown primary melanoma patients. Patients will be randomized 1:1 to receive either 2 cycles
of neoadjuvant ipilimumab 80 mg + nivolumab 240 mg every 3 weeks followed by a total lymph
node dissection (TLND) and, if applicable, resection of in-transit metastases (arm A) versus
standard upfront TLND +/- resection of in-transit metastases followed by 12 cycles adjuvant
nivolumab 480 mg every 4 weeks (arm B). Patients not achieving a pathologic response in arm A
will also receive adjuvant nivolumab 480 mg every 4 weeks for 46 weeks (11 cycles). In case
of BRAF V600E/K mutation-positivity, patients from arm A not achieving a pathologic response
(>50% viable tumor) will be treated with adjuvant dabrafenib plus trametinib for 46 weeks.
Patients will be treated in the study in both arms until melanoma progression to irresectable
stage III or stage IV disease, disease recurrence, unacceptable toxicity, subject withdrawal
of consent or until end of study treatment.
An interim analysis will be performed after 60 events have occurred. The data safety monitory
board (DSMB) will be ad hoc consulted when unexpected toxicities are reported. Patients will
be followed by 12 weekly CT scans until end of year 3 and then until year 5 according to the
institute's standards.