Abstract 1072P
Background
The aim of neo-adjuvant therapy in locally advanced or oligometastatic melanoma is to facilitate radical resection, improve outcomes and undertake research to identify biomarkers of response and resistance. We investigate the efficacy of Ipilimumab/Nivolumab combination as primary treatment of locally advanced or oligometastatic melanoma patients (pts), within an open label, single arm study.
Methods
Treatment consists in 4 neoadjuvant cycles of Ipilimumab 1 mg/kg and Nivolumab 3 mg/kg every 3 weeks, followed by surgery and adjuvant Nivolumab 480 mg every 4 weeks for 6 cycles. Primary objective is pathological complete remission (pCR) rate, according to Neoadjuvant Melanoma Consortium criteria. Secondary objectives are: safety, feasibility and efficacy; QoL; identification of molecular and immunological biomarkers of response and resistance, degree of immune activation; evaluation of microbioma.
Results
35 pts were treated within the trial: 3 pts are still in neoadjuvant therapy, 3 pts were discontinued before surgery (due to toxicity, progression and consent withdrawal) and 29 pts concluded neoadjuvant therapy after 4 (26 pts), 3 (2 pts) and 2 (1 patient) cycles and underwent surgery. pCR was reached in 16 (55%), near pCR in 2 (7%), pathological partial remission in 4 (14%) and pathological no response (pNR) in 4 (14%) pts. 21 pts concluded the adjuvant therapy. With a median follow-up of 12 months, 34 pts are alive. Relapses occurred in 1 patient after the 4 courses of neoadjuvant and in 4 pts (1 pCR and 3 pNR at surgery) during/after adjuvant therapy. 6 pts (17%) developed related G3-4 adverse events (AE): 3 transaminitis, 1 pneumonitis, 1 myocarditis and 1 CPK increase; all of them but one underwent to surgery after toxicity resolution. One patient died 5 months after the end of therapy due to ischemic stroke.
Conclusions
Neoadjuvant Ipilimumab/Nivolumab followed by adjuvant nivolumab is safe and able to achieve a pCR/near pCR rate of 62%. Toxicity was lower than that already observed with this schedule. Translational data on potential genomic biomarkers of response, gut microbiome and systemic inflammatory landscape evaluated longitudinally on each patient will be presented at ESMO.
Clinical trial identification
EudraCT 2018-002172-40.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BMS.
Disclosure
M.T. Fierro: Financial Interests, Personal, Invited Speaker: Novartis BMS, MSD, Pierre Fabre. F. Picciotto: Financial Interests, Personal, Invited Speaker: Novartis BMS, MSD. V. Caliendo: Financial Interests, Invited Speaker: Novartis BMS, MSD. P. Quaglino: Financial Interests, Personal, Advisory Board: Novartis, BMS, MSD, Pierre Fabre . P.F. Ferrucci: Financial Interests, Invited Speaker: from Novartis, BMS, MSD; Pierre Fabre, Roche. All other authors have declared no conflicts of interest.