Abstract 1147P
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. Recently, pathological response has been indicated as a surrogate of survival. 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, two centres study.
Methods
Treatment schedule 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. Secondary objectives are: safety, feasibility and efficacy; health related quality of life; identification of molecular and immunological biomarkers of response and resistance (somatic genetic drivers, tumor mutational burden (TMB), mutational signatures, predicted neoantigens, germline HLA typing, somatic HLA mutations and liquid biopsy); degree of immune activation; evaluation of microbioma.
Results
From March 2019, 26 out of 35 pts were enrolled. In the ITT population (22 pts), 21 pts were stage III and 1 stage IV-M1b cutaneous melanoma; 17 pts concluded neoadjuvant therapy and received surgery; 4 pts concluded the adjuvant treatment. pCR was reached in 9/17 (52%), pathological partial remission in 4/17 (24%) and pathological no response (pNR) in 4/17 (24%) pts. With a median follow-up of 5 months, all pts are alive; one, with pNR at surgery, relapsed during adjuvant phase. In the neoadjuvant phase 4 pts (18%) developed G3-4 adverse events (AE): 2 transaminitis, 1 myocarditis and 1 asyntomatic CPK increase after 4, 3 and 2 cycles; 3 of them underwent to surgery after toxicity resolution. No G3-4 AE were observed during adjuvant phase.
Conclusions
Primary Ipilimumab/Nivolumab is effective and feasible, showing high pCR rate. Toxicity was superimposable to that already observed with this schedule. Longer follow-up is needed to assess a correlation between pathological response and survival. Translational data will be available and presented at ESMO.
Clinical trial identification
EudraCT: 2018-002172-40.
Editorial acknowledgement
Legal entity responsible for the study
Pier Francesco Ferrucci.
Funding
Bristol-Mayer Squibb.
Disclosure
E. Cocorocchio: Advisory/Consultancy: Array; Speaker Bureau/Expert testimony: Roche. P. Queirolo: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Merk; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sun Pharma. M.T. Fierro: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre-Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. P. Quaglino: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre-Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. P.F. Ferrucci: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.