Trial results for the Phase 1/2 study (NCT04688658) investigating nivolumab in combination with duvelisib for patients with advanced unresectable melanoma were posted on ClinicalTrials.gov on 2025-12-17. The study reported no dose-limiting toxicities (DLTs) across both dose cohorts, with an overall response rate of 0.20 observed in the duvelisib 15mg + nivolumab 240mg arm.
Background
The trial aimed to evaluate the combination of duvelisib and nivolumab in patients with advanced unresectable melanoma who had progressed on prior anti-PD1 therapy. The study sought to determine the Recommended Phase II Dose of oral duvelisib when administered with intravenous nivolumab.
Trial design
The study (NCT04688658) was a Phase 1/2, open-label trial that enrolled 13 participants with advanced unresectable melanoma who had progressed on anti-PD1 therapy. Participants received either duvelisib 15mg or duvelisib 25mg, both in combination with nivolumab 240mg. Treatment was administered for up to 1 year or until disease progression or unacceptable side effects. The trial was terminated.
Key results
For the outcome of "DLTs by Phase I Dose of Duvelisib With Nivolumab", both the duvelisib 15mg + nivolumab 240mg group and the duvelisib 25mg + nivolumab 240mg group reported 0 participants experiencing dose-limiting toxicities.
Regarding "Best Overall Response Rate (ORR)", the duvelisib 15mg + nivolumab 240mg group showed an ORR of 0.20 (proportion of patients). The duvelisib 25mg + nivolumab 240mg group showed an ORR of 0.0 (proportion of patients).
For "Best Overall Response" counts, the duvelisib 15mg + nivolumab 240mg group had 1 participant, 1 participant, and 3 participants across different response categories. The duvelisib 25mg + nivolumab 240mg group had 0 participants, 1 participant, and 3 participants.
For "Change in CD 8+ TIL Frequency", the duvelisib 15mg + nivolumab 240mg group had a mean change of -0.87 percentage of cells (Standard Deviation: 2.91). The duvelisib 25mg + nivolumab 240mg group showed a mean change of 2.66 percentage of cells (Standard Deviation: 3.65).
What this means
The results of this Phase 1/2 trial suggest that the combination of duvelisib and nivolumab was generally well-tolerated at the tested doses in patients with advanced unresectable melanoma, as indicated by the absence of dose-limiting toxicities. However, the observed overall response rates were low, with 0.20 in the 15mg duvelisib arm and 0.0 in the 25mg duvelisib arm. The trial's termination, combined with the limited efficacy signals, suggests that further development of this specific combination in this population might be limited, despite the favorable safety profile observed in this small cohort.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04688658, titled "Duvelisib in Combination With Nivolumab in Patients With Advanced Unresectable Melanoma," were posted on 2025-12-17 on clinicaltrials.gov.