Trial results for the Phase 1 study NCT03388632, investigating nivolumab and ipilimumab in combination with recombinant interleukin-15 (rhIL-15) for people with refractory cancers, were posted on ClinicalTrials.gov on 2025-12-03. The study determined a maximum tolerated dose (MTD) of 1.0 mcg/kg/day for rhIL-15 in the triplet combination, with zero dose-limiting toxicities observed across all tested arms.
Background
The study investigated the combination of recombinant interleukin-15 (rhIL-15) with checkpoint inhibitors nivolumab and ipilimumab in patients with metastatic solid tumors and treatment-refractory cancers. Interleukin-15 (IL-15) is known to activate the immune system, while nivolumab and ipilimumab are designed to unblock immune cells. The rationale for this combination is to potentially enable immune cells to recognize and attack cancer cells, leading to tumor shrinkage.
Trial design
The Phase 1 study (NCT03388632) was a completed trial designed to evaluate the effects and determine the maximum dose of recombinant interleukin-15 (rhIL-15) when administered in combination with nivolumab and ipilimumab. The study enrolled 31 participants aged 18 and older who had metastatic solid tumors or treatment-refractory cancers. Participants were screened for medical history, physical exam, heart, blood, and urine tests, and scans, including tumor biopsy.
Key results
The primary objective of determining the maximum tolerated dose (MTD) and assessing dose-limiting toxicities (DLTs) was met. For the outcome "Maximum Tolerated Dose (MTD) at Which Dose-Limiting Toxicities (DLT) Occurred With rhIL-15 Administered in Combination With Fixed Doses of Nivolumab and Ipilimumab," the MTD in the escalation phase of Arm C (triplet combination) was determined to be 1.0 mcg/kg/day.
Importantly, the study reported zero dose-limiting toxicities across all evaluated arms and dose levels for the outcome "Number of Dose-limiting Toxicities (DLT) Possibly, Probably, or Definitely Related to Study Drugs." This included:
- Arm A Doublet A (rhIL-15 0.5mcg/kg & Nivolumab 240mg): 0 toxicities
- Arm B Doublet B (rhIL-15 0.5mcg/kg & Ipilimumab 1mg/kg): 0 toxicities
- Arm C Triplet 1 (rhIL-15 0.5mcg/kg/Nivolumab 240mg/Ipilimumab 1mg/kg): 0 toxicities
- Arm C Triplet 2 (rhIL-15 1mcg/kg/Nivolumab 240mg/Ipilimumab 1mg/kg): 0 toxicities
- Arm C Triplet 3 (rhIL-15 2mcg/kg & Nivolumab 240mg/Ipilimumab 1mg/kg): 0 toxicities
The consistent absence of DLTs suggests a favorable safety profile for the tested doses of rhIL-15 in these combinations.
What this means
The results from this Phase 1 study provide crucial safety and tolerability data for the combination of recombinant interleukin-15 (rhIL-15) with nivolumab and ipilimumab in patients with refractory cancers. The identification of a maximum tolerated dose of 1.0 mcg/kg/day for rhIL-15 in the triplet regimen, coupled with the observation of zero dose-limiting toxicities across all tested arms, indicates that this combination is well-tolerated at these dose levels. These findings support the potential for further clinical development to investigate the efficacy of this triple combination in treating advanced cancers.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03388632, titled "Recombinant Interleukin-15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in People With Refractory Cancers," were posted on 2025-12-03 on clinicaltrials.gov.