Phase 1 clinical trial evaluating the safety and efficacy of combined therapy with nivolumab and ipilimumab in patients with advanced melanoma

The aim of this phase 1 clinical trial was to assess the safety and efficacy of combined therapy with nivolumab and ipilimumab (Yervoy) in patients with advanced melanoma.

Advanced melanoma is cancer of the pigmented (colored) cells of the skin (or "melanocytes") that has spread to distant lymph nodes or other organs of the body. Treatment for this stage of melanoma may include surgery, chemotherapy, radiotherapy and immunotherapy (biological therapy). Immunotherapy stimulates the patient’s own immune system to recognize and destroy cancer cells. Ipilimumab is an immunotherapy drug approved by the U.S. FDA for the treatment of patients with advanced melanoma. It has been shown that ipilimumab prolongs survival for these patients. Nivolumab is another immunotherapy drug currently being tested in clinical trials, which shows promise in shrinking the size of the cancer. This study tested if the combination of the two drugs is has more benefits than each drug alone in patients with advanced melanoma.

This study included 86 patients with melanoma. 53 patients (73%) received ipilimumab and nivolumab together (the combined treatment group), while 33 received first ipilimumab and, after 4 to 12 weeks from the last dose, they were given nivolumab (the sequential treatment group). Among the patients with combined treatment, 93% had side effects. The most common side effects reported were rash, tiredness and diarrhea. In the other group, side effects were reported by 73% of the patients and the most frequent was itching. All side effects were generally manageable. 65% of the patients in the combined treatment group responded to the treatment (clinical response). Of these, 53% had an 80% reduction in the size of the cancer. From the sequenced treatment group, only 13% had an 80% reduction in cancer size.

In conclusion, combined therapy with ipilimumab and nivolumab was safely used, with manageable side effects, in patients with advanced melanoma. Moreover, patients treated with the combined therapy had higher clinical response compared to those in the sequential treatment.

The results of this study should be taken with caution because of the small number of patients and the patient selection. This was only a phase 1 clinical trial evaluating the safety and efficacy of this drug combination. Phase 2 and 3 clinical trials are currently being done to confirm the findings of this study. As it is still under research, nivolumab is not yet approved by the U.S. FDA.

This study was funded by Bristol-Myers Squibb, the manufacturer of nivolumab.