NCT07219576

Retifanlimab and Ruxolitinib In Solid Malignancies

PRISM: Phase 1b of Retifanlimab and Ruxolitinib In Solid Malignancies Progressing on Prior Checkpoint Inhibition

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn what dose of ruxolitinib can be given safely together with retifanlimab in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma. The main question it aims to answer is: What is the maximum dose of ruxolitinib that can be used safely in patients with metastatic renal cell carcinoma and non-small cell lung carcinoma, and will it work? Participants will: Take drug ruxolitinib twice a day and keep a diary of when they take ruxolitinib at home; visit the clinic for infusions of retifanlimab every 4 weeks; visit the clinic for checkups and tests.

Detailed description

The treatment landscape for renal cell carcinoma has evolved significantly with the use of immunotherapy. Immune checkpoint inhibitors are now used in both adjuvant and metastatic settings. Programmed cell death protein-1 (PD-1) inhibitors are utilized as adjuvant therapy following nephrectomy for high-risk disease, and in the metastatic setting as first-line treatment in combination with either cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition or vascular endothelial growth factor (VEGF) pathway blockade. Despite improvements in overall survival with these approaches, the majority of patients develop either intrinsic or acquired resistance, necessitating subsequent therapy. The optimal management of patients progressing on immunotherapy remains an important unmet need in renal cell carcinoma. Also the therapeutic landscape for non-small cell lung cancer has been transformed by immunotherapy, with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors now established as standard first-line therapy either as monotherapy for patients with high PD-L1 expression (≥50%) or in combination with chemotherapy regardless of PD-L1 status. Despite significant improvements in survival outcomes, most patients eventually develop resistance to PD-1/PD-L1 blockade. The optimal approach for non-small cell lung cancer progressing on immunotherapy remains unclear. The identification of effective treatment strategies for patients with immunotherapy-resistant non-small cell lung cancer represents a critical unmet need, particularly given the large patient population affected by this disease. Ex vivo experiments by the investigators showed that Janus kinase inhibitors restore cytokine production and proliferation of exhausted T cells and that the Janus kinase 1/2 inhibitor ruxolitinib enhanced the efficacy of immune checkpoint inhibitors in cancer models. Also a preliminary clinical trial by the investigators showed encouraging results, inasmuch 10 of 19 evaluable patients responded to therapy with the Janus kinase 1/2 inhibitor ruxolitinib plus the programmed cell death protein-1 blocker nivolamab. Among the patients who responded, six had complete responses and additional two experienced an indeterminate response or stable disease. Building on previous clinical trials, the investigators plan to use the Janus kinase 1/2 inhibitor ruxolitinib in combination with the PD-1 blocker retifanlimab in renal cell carcinoma and non-small cell lung cancer, two tumor types in which PD-1 blockers are effective at least in a subset of patients.

Conditions

• Non Small Cell Lung Carcinoma
• Renal Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Ruxolitinib	Janus kinase 1/2 inhibitor
DRUG	Retifanlimab	Programmed cell death protein-1 blocker

Timeline

• Start date: 2026-01-08
• Primary completion: 2027-12-01
• Completion: 2029-12-01
• First posted: 2025-10-22
• Last updated: 2026-01-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study