Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma

Phase I/II Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma

This is a Phase I/II, open-label, multi-center study of axitinib in combination with nivolumab in patients with previously treated and untreated advanced RCC. This clinical study will be composed of a dose finding phase (Phase I) and two parallel dose expansion phases (Phase II). The dose finding phase will assess the safety of the combination and establish a recommended phase II dose (RP2D, the highest tested dose that is declared safe and tolerable by the Investigators and the Sponsor Investigator) in patients with advanced RCC who have received prior systemic therapy for metastatic disease. Phase II will evaluate the efficacy of the combination at the RP2D in two parallel expansion cohorts in both previously treated and treatment naïve patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Axitinib

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins
  • New York
    • Albany, New York, United States, 12206
      • US Oncology and Hematology
    • New York, New York, United States, 10021
      • Cornell
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed advanced RCC with predominantly clear cell subtype.
• Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study.
• Formalin fixed, paraffin embedded [FFPE] tissue block(s) or at least 12 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
• At least one measurable lesion as defined by RECIST version 1.1.
• Age > 18 years.
• ECOG performance status 0 or 1
• Adequate bone marrow, kidney, and liver function as defined by: WBC ≥ 2000/μL. Neutrophils ≥ 1500/μL. Platelets ≥ 100 x103/μL. Hemoglobin > 9.0 g/dL. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula): Female CrCl = (140 - age in years) x (weight in kg x 0.85)/(72 x serum creatinine in mg/dL). Male CrCl = (140 - age in years) x (weight in kg x 1.00)/(72 x serum creatinine in mg/dL). AST/ALT ≤ 3 x ULN. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
• No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure (BP) readings taken at least 1 hour apart. The baseline systolic BP readings must be ≤ 150 mm Hg, and the baseline diastolic BP readings must be ≤ 90 mm Hg
• Patients enrolled to the prior treatment arm of the expansion cohort must have been exposed to a TKI for metastatic disease OR treated with the combination of ipilimumab and nivolumab in the 1st line setting for metastatic disease. Exposure to TKI as part of (neo)adjuvant treatment that completed within 1 year of study qualifies as prior exposure as well. Prior high dose interleukin-2 is allowed and patients who received this as their only prior line of treatment for metastatic disease may be included in the treatment naïve group.

Exclusion Criteria:

• Prior therapy with axitinib
• Prior systemic therapy directed at advanced RCC is not allowed for patients enrolled to the expansion cohort, treatment naïve arm. If prior (neo)adjuvant treatment given as part of a clinical trial, this would be allowed as long as last dose was > 1 year prior to start of treatment
• Patients enrolled to the prior treatment arm of the dose escalation cohort must not have received anti-cancer therapy less than 14 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.
• Patients are excluded if they have active, symptomatic brain metastases or leptomeningeal metastases. Subjects with known brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for four weeks (after treatment is complete and within 28 days prior to study drug administration.
• Second malignancy requiring active systemic treatment
• Diagnosis of immunodeficiency
• Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Major surgery <4 weeks or radiation therapy <2 weeks of study entry. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• Gastrointestinal abnormalities including: Inability to take oral medication; Requirement for intravenous alimentation; Prior surgical procedures affecting absorption including total gastric resection; Treatment for active peptic ulcer disease in the past 6 months; Active gastrointestinal bleeding as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; Malabsorption syndromes.
• Evidence of inadequate wound healing.
• Active bleeding disorder or other history of significant bleeding episodes within 30 days before study entry.
• Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
• Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4/5 inhibitors including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
• Current use or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
• As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen.
• Known hepatitis B virus (HBV) or hepatitis C virus (HBV) infection.
• Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• History of any of the following cardiovascular conditions within 12 months of screening: Myocardial infarction, Unstable angina pectoris, Cardiac angioplasty or stenting, Coronary/peripheral artery bypass graft, Class III or IV congestive heart failure per New York Heart Association, Cerebrovascular accident or transient ischemic attack
• History of deep vein thrombosis or pulmonary embolism within 6 months of screening. Patients who are currently taking anticoagulation therapy for a prior history (> 6 months from screening) of thrombosis may still be eligible.
• Pregnant or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I patients; Phase I patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.	Drug: Nivolumab; PD-1 inhibitor; Drug: Axitinib; Tyrosine kinase inhibitor
Experimental: Phase II patients: cohort 1; Phase II cohort 1 patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.	Drug: Nivolumab; PD-1 inhibitor; Drug: Axitinib; Tyrosine kinase inhibitor
Experimental: Phase II patients: cohort 2; Phase II cohort 2 patients must not have received prior systemic therapy for advanced RCC.	Drug: Nivolumab; PD-1 inhibitor; Drug: Axitinib; Tyrosine kinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	To be assessed by RECIST 1.1	Up to 12 months
Incidence of treatment-related adverse events	To be assessed by CTCAE v4.03. Will be used to establish recommended phase II dose (RP2D)	Up to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR is the time from first partial response or complete response until progressive disease as assessed by RECIST 1.1	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks
Progression free survival (PFS)	PFS is the time from initiation of treatment to confirmed disease progression per RECIST 1.1	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks
Overall survival (OS)	OS is the time from initiation of treatment to death or when the patient is lost to follow up	From date of initiation of treatment to death or when the patient is lost to follow up, approximately 25 months on average
Safety profile as assessed by CTCAE 4.03	Summarized by type, frequency, and severity	Up to 15 months
PD-L1 expression on tumor biospecimens	Descriptive statistics from analysis of patient samples	Up to 12 months
Tumor infiltrating lymphocyte assessments on tumor biospecimens	Descriptive statistics from analysis of patient samples	Up to 12 months
Pharmacodynamic effect of study treatment including cytokines	Descriptive statistics from analysis of patient samples	Up to 12 months

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Estimated): November 6, 2026
• Study Completion (Estimated): April 6, 2027

Study Registration Dates

• First Submitted: April 11, 2017
• First Submitted That Met QC Criteria: May 30, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Benzene Derivatives; Acids, Carbocyclic; Benzoates; Benzamides; Indazoles; Pyrazoles; Nivolumab; Axitinib
• Other Study ID Numbers: GU-102; 17-1009 (Other Identifier: Fox Chase Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No