Safety and efficacy of intravenous nivolumab with either intratumoral or intravenous ipilimumab in previously untreated metastatic melanoma

Intravenous administration of anti-CTLA4 plus anti-PD1 provides durable tumor responses but causes severe treatment-related adverse events in patients with cancer. Intratumoral adminstration at lower doses but high local concentrations could enhance antitumor efficacy while minimzing systemic exposure and toxicity. The phase 1b NIVIPIT trial, at four centers in France, enrolled 61 patients with previously untreated metastatic melanoma, randomly assigned 2:1 to receive intravenous nivolumab (anti-PD1) combined with either intratumoral ipilimumab (anti-CTLA4; 0.3 mg/kg) or intravenous ipilimumab (3 mg/kg). The primary endpoint was met with significantly lower incidence of grade 3 or 4 treatment-related adverse events at 6 months (22.6% in the intratumoral arm versus 57.1% in the intravenous arm). RECIST best objective response rate reached 65.7% for ipilimumab injected lesions and 50% for uninjected lesions. The authors conclude that these results provide a rationale for intratumoral anti-CTLA4 strategies in oligometastatic and early-stage cancers.