Trial results for the Phase 2 study (NCT04493203) investigating nivolumab plus axitinib in patients with anti-PD1 refractory advanced melanoma were posted on ClinicalTrials.gov on 2025-07-15. The study reported an overall response rate (ORR) of 10 percentage of patients for the combination therapy in this patient population.
Background
The trial investigated nivolumab, an anti-PD1 therapy, in combination with axitinib for patients with unresectable stage III or IV melanoma. This patient population had previously progressed on anti-PD1 therapy, either alone or with concomitant anti-CTLA4 therapy, indicating a refractory disease state.
Trial design
The study (NCT04493203) was a Phase 2 trial that enrolled 31 participants with unresectable stage III or IV melanoma. All patients had progressed on prior anti-PD1 therapy, with or without anti-CTLA4 therapy. Participants received treatment with nivolumab 480 mg intravenously every 4 weeks and axitinib 5 mg twice daily by mouth. Treatment was planned for up to two years in the absence of disease progression or dose-limiting toxicities.
Key results
The trial evaluated the overall response rate (ORR) and disease control rate (DCR) for the combination of nivolumab plus axitinib. Key findings include:
- The overall response rate (ORR) for the entire cohort was 10 percentage of patients.
- For patients with prior ipilimumab/nivolumab treatment, the ORR was 6.3 percentage of patients.
- For patients with no prior ipilimumab/nivolumab treatment, the ORR was 13.3 percentage of patients.
- Patients with 3 or fewer prior lines of therapy had an ORR of 15 percentage of patients.
- Patients with more than 3 prior lines of therapy had an ORR of 0 percentage of patients.
- The ORR for patients with secondary IO resistance was 18.8 percentage of patients, while for those with primary IO resistance, it was 0 percentage of patients.
- By histology, the ORR was 14.3 percentage of patients for acral melanoma, 5.9 percentage of patients for cutaneous melanoma, and 14.3 percentage of patients for mucosal melanoma.
- The disease control rate (DCR) for the overall cohort was 45.2 percentage of patients.
What this means
The results from this Phase 2 trial suggest that the combination of nivolumab and axitinib may offer limited clinical benefit in heavily pre-treated patients with anti-PD1 refractory advanced melanoma, particularly those with more than three prior lines of therapy or primary IO resistance, where the ORR was 0%. However, a modest response was observed in specific subgroups, such as those with secondary IO resistance (18.8% ORR) or fewer prior lines of therapy (15% ORR), and a disease control rate of 45.2% indicates some stabilization of disease. These findings highlight the challenges in treating this refractory patient population and suggest that patient selection based on prior treatment history and resistance mechanisms may be important for future studies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04493203, titled "Nivolumab Plus Axitinib in Patients With Anti-PD1 Refractory Advanced Melanoma," were posted on 2025-07-15 on clinicaltrials.gov.