Neo-adjuvant Immunotherapy in Patients With Localized Melanoma

The combination of ipilimumab + nivolumab injected intravenously before resection of resectable stage III melanoma is more effective than adjuvant immunotherapy as recently demonstrated in a large phase III randomized controlled trial. However, the dual systemic immunotherapy gives rise to severe AEs (30% of patients had \> grade 3 related AEs versus 14% in the adjuvant arm). NEO-1, a prospective, multicenter, phase II sub-protocol of the NEOREM master protocol (NCT07262489) focuses on evaluating the efficacy and safety of intratumoral neo-adjuvant treatment with ipilimumab and nivolumab in patients with resectable stage III melanoma. NEO-1 is a proof-of-concept study designed to validate human intratumoral immunotherapy (HIT-IT) approach, which could maximize its dose/efficacy ratio of combined ipilimumab and nivolumab treatment while preventing systemic AEs. Image guided drug administration directly into tumor will increase the drug concentration at the tumor site leading to targeted drug action. While evaluating the efficacy of intratumoral administration of ipilimumab in combination with nivolumab in melanoma patients, the NEO-1 study employs PORTRAIT profiling to analyze fresh blood and tumor samples collected at baseline and throughout treatment. This approach will reveal the features of the tumor microenvironment both before and after surgery, facilitating the identification of biomarkers that predict the efficacy of the proposed immunotherapy. The NEOREM master protocol (NCT07262489) allows the rapid analyses of the fresh samples collected, which enables an actual characterization of the immune landscape in patients prior to and during treatment.