S1801: A randomized phase II trial of adjuvant versus neoadjuvant pembrolizumab (PEM) for melanoma.

Abstract

TPS10090 Background: Although long term outcomes for most patients with early-stage melanoma is excellent following surgery, patients who have high-risk features such as lymph node involvement have poorer outcomes. Adjuvant therapy (AT) is currently considered for patients with stage III melanoma and selected patients with resected stage IV melanoma. Currently, AT for melanoma is anti-PD-1 or targeted therapy in the presence of a BRAF mutation. At this time we are not able to predict which patients will derive benefit from AT and experience cure. While curative surgery is the goal of early treatment of primary melanoma, some cases with bulky nodal involvement are at high risk of local or distant recurrence despite upfront surgery. Neoadjuvant treatment (NAT) offers the benefit of an early on-treatment pathological sample that can be profiled for biomarkers and correlated with survival. Treating with anti-PD1 while tumor transiently remains in the body may generate a stronger immune response from tumor-infiltrating lymphocytes against in vivo tumor antigens compared to the traditional adjuvant setting where antigen is presented by microscopic residual tumor burden. Pilot studies using NAT with have been initiated in melanoma. Multidisciplinary coordination in these cases is paramount. In these studies, an improvement in relapse-free survival and overall survival has been observed; additionally, pathologic response rates to NAT have been estimated in small studies. Methods: S1801 is a randomized phase II study of AT versus NAT with PEM (NCT03698019). Patients with measurable, clinically detectable and resectable cutaneous, acral, and mucosal melanomas without brain metastasis are eligible. Patients are randomized 1:1 to the AT or the NAT. Patients getting AT receive surgery first followed by 18 doses of PEM 200 mg IV every 3 weeks. Patients getting NAT receive 3 doses of pre-operative PEM followed by surgery and then 15 doses of adjuvant PEM. Radiation may be given on either arm after surgery, at the investigator’s discretion. Primary endpoint is event-free survival measured from the date of randomization to the date of first documented progression that renders the patient unable to receive planned protocol surgery, failure to begin AT within 84 days of surgery, relapse after surgery, or death due to any cause. Safety monitoring is conducted with disease progression and toxicity thresholds. The key Translational Medicine objective of this trial is to determine the pathologic response rate to NAT with 3 doses of PEM. Enrollment is at 94 of a planned 500 patients. Clinical trial information: NCT03698019.