Retifanlimab and Ruxolitinib In Solid Malignancies

NCT07219576 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 812209
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non Small Cell Lung Carcinoma; Renal Cell Carcinoma

Keywords

programmed death ligand-1 blocker; Janus kinase inhibitor; 3+3 dose escalation design; recommended phase 2 dose

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose

  Determine the recommended phase 2 dose of ruxolitinib in combination with a fixed dose of retifanlimab. The recommended phase 2 dose will be determined by assessment of the dose limiting toxicities during the first cycle of treatment.

  28 days

Study Arms (1)

ruxolitinib plus retifanlimab

EXPERIMENTAL

Combination of the Janus kinase 1/2 inhibitor ruxolitinib plus the programmed cell death protein-1 blocker retifanlimab. The study utilizes a standard 3+3 dose escalation design evaluating 2 dose escalation levels (15 mg and 20 mg orally twice daily) and 2 dose de-escalation levels (10 mg and 5 mg orally twice daily, if necessary) of ruxolitinib with fixed dose retifanlimab (500 mg intravenously every 4 weeks), followed by an expansion cohort at the recommended phase 2 dose.

Drug: Ruxolitinib; Drug: Retifanlimab

Interventions

Ruxolitinib DRUG

Janus kinase 1/2 inhibitor

Also known as: Jakafi, Jakavi

ruxolitinib plus retifanlimab

Retifanlimab DRUG

Programmed cell death protein-1 blocker

Also known as: Zynyz

ruxolitinib plus retifanlimab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced or metastatic clear cell renal cell carcinoma or non-small cell lung carcinoma having progressed on prior PD-1/PD-L1 therapy (radiographic progression within 6 months of discontinuing immunotherapy; immunotherapy does not need to be the immediate line of preceding therapy).
• Decline standard of care treatment or no available standard of care treatment.
• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate organ and marrow function:
• Absolute neutrophil count ≥ 1.0×10\^9/L.
• Platelet count ≥ 100×10\^9/L.
• Hemoglobin level ≥ 8.5 g/dL; criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 2 weeks.
• Serum creatinine ≤ 2 mg/dL (or estimated creatinine clearance ≥ 30 mL/minute calculated by the Cockcroft Gault or Modification of Diet in Renal Disease formulas).
• Aspartate Aminotransferase and Alanine Aminotransferase ≤ 2.5 x upper limit of normal.
• Bilirubin ≤1.5 x upper limit of normal.
• Ability to take oral medication and be willing to adhere to the study intervention.
• Willingness to comply with all study procedures and availability for the duration of the study.

You may not qualify if:

• Pregnancy or lactation.
• No prior treatment with Janus kinase inhibitors.
• No more than one prior line of PD-1/PD-L1 therapy. No limit on prior lines of systemic therapy. PD-1/PD-L1 therapy does not need to be the most immediate prior line of therapy. Patients with progressive disease as best response to prior PD-1/PD-L1 therapy are not eligible. Need to have either stable disease, partial response, or complete response as best response using RECIST version 1.1 principles to prior PD-1/PD-L1 therapy.
• Received systemic anti-cancer therapy within 3 weeks of enrollment or small molecule kinase inhibitors within two weeks or six elimination half-lives of enrollment, whichever is sooner.
• Has received prior radiotherapy within one week before enrollment.
• Has had history of major surgery less than two weeks before enrollment. Adequate wound healing after major surgery must be assessed clinically.
• Failure to recover from any immune related adverse event from prior immunotherapy to Common Terminology Criteria in Adverse Event grade ≤ 1 (participants with grade ≤ 2 sensory neuropathy, endocrinopathies controlled by hormone replacement, or other grade ≤ 2 not constituting a safety risk based on investigator's judgment are eligible).
• Known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate, provided they are clinically stable and without the requirement of steroid treatment for at least 14 days prior to enrollment.
• Known active or history of autoimmune disease that requires steroids or immunosuppressive agents. Patients are allowed in the study if they have vitiligo, type 1 diabetes mellitus, controlled asthma; residual hypo- or hyperthyroidism due to an autoimmune condition not requiring immunosuppressive treatment; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without steroids or immunosuppressive agents; or arthritis that is managed without systemic therapy beyond oral acetaminophen and non-steroidal anti-inflammatory drugs.
• Diagnosis of immunodeficiency or receiving systemic steroid therapy (equivalent of prednisone \> 10 mg daily) or any other form of immunosuppressive therapy within seven days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids is permitted. Intra-articular, intra-ocular, intra-nasal, inhalation and ocular steroids are permitted.
• Active infections requiring systemic antibiotics or antifungal or antiviral treatment within 7 days before first dose of study treatment.
• Active tuberculosis.
• Active immunodeficiency virus (HIV) infection. To be enrolled, patients with history of HIV must have an undetectable viral load at screening.
• Active hepatitis B or hepatitis C virus infections. To be enrolled, patients with a history of these infections must have been treated and cured with undetectable viral load at screening.
• Have clinically significant cardiovascular disease defined as:

Sponsors & Collaborators

• University of California, San Diego: lead
• Incyte Corporation: collaborator

Study Sites (1)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Rana McKay

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rana McKay, MD

CONTACT

(858) 822-5354; cancerCTO@health.ucsd.edu

Alexandrea Cronin

CONTACT

(858) 822-5354; cancerCTO@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 20, 2025
• First Posted: October 22, 2025
• Study Start: January 8, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)