A phase 1 trial evaluated the safety and clinical activity of combined PD-1 (nivolumab) and CTLA-4 (ipilimumab) blockade in advanced melanoma patients. The study included 53 patients receiving concurrent treatment and 33 receiving sequenced treatment. The objective response rate (ORR) was 40% for concurrent treatment, with 65% of patients showing clinical activity, including 53% achieving an objective response with ≥80% tumor reduction. Grade 3–4 adverse events occurred in 53% of concurrent patients, but were generally reversible. For sequenced treatment, 18% had grade 3–4 adverse events and the ORR was 20%. The combination showed rapid and deep tumor regressions, with 31% of patients achieving ≥80% tumor regression by week 12. The safety profile was manageable, with no treatment-related deaths. The results suggest that combined PD-1 and CTLA-4 blockade may offer superior clinical activity compared to monotherapy, with durable responses and a favorable safety profile. The study supports further investigation in larger trials to confirm these findings.A phase 1 trial evaluated the safety and clinical activity of combined PD-1 (nivolumab) and CTLA-4 (ipilimumab) blockade in advanced melanoma patients. The study included 53 patients receiving concurrent treatment and 33 receiving sequenced treatment. The objective response rate (ORR) was 40% for concurrent treatment, with 65% of patients showing clinical activity, including 53% achieving an objective response with ≥80% tumor reduction. Grade 3–4 adverse events occurred in 53% of concurrent patients, but were generally reversible. For sequenced treatment, 18% had grade 3–4 adverse events and the ORR was 20%. The combination showed rapid and deep tumor regressions, with 31% of patients achieving ≥80% tumor regression by week 12. The safety profile was manageable, with no treatment-related deaths. The results suggest that combined PD-1 and CTLA-4 blockade may offer superior clinical activity compared to monotherapy, with durable responses and a favorable safety profile. The study supports further investigation in larger trials to confirm these findings.