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Clear Cell Renal Cell CarcinomaPhase 2NCT03092856

Axitinib With or Without Anti-OX40 Antibody PF-04518600 in Treating Patients With Metastatic Kidney Cancer

A Phase 2 study testing Anti-OX40 Antibody PF-04518600, Axitinib and Laboratory Biomarker Analysis in people with Clear Cell Renal Cell Carcinoma and Metastatic Renal Cell Cancer, run by University of Southern California at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This randomized phase II trial studies how well axitinib with or without anti-OX40 antibody PF-04518600 work in treating patients with kidney cancer that has spread to other parts of the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-OX40 Antibody PF-04518600, Axitinib and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
62 participants
Where
9 sitesUnited States
Study dates
19 Jul 2017to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide informed consent
  • Histological confirmation of renal cell carcinoma (RCC) with a predominantly (> 50%) clear cell component
  • Metastatic RCC
  • Must have had a nephrectomy (radical or partial) and must provide the cell block from the nephrectomy
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria
  • Must have progression of disease within 6 months of study enrollment after treatment with only one of the following:
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  • Two prior lines of therapy: a VEGF inhibitor (other than axitinib), followed by a single agent PD-1/PDL-1 antibody, or
  • One prior line of therapy: combination of a VEGF inhibitor (other than axitinib) AND a PD1/PDL1 antibody, or
  • Additional prior systemic treatments not allowed
  • Must agree to a fresh core or excisional biopsy from a metastatic site within a 12-week window prior to enrollment; if such a biopsy is already available, cell blocks must be provided; (Note: fine needle aspiration [FNA] and bone metastases samples are not acceptable for submission); specimens from the nephrectomy and fresh biopsy must be received and assessed for adequacy of tissue by the Data Coordinating Center (DCC) (University of Southern California [USC]) prior to randomization
  • Zubrod performance status of =< 2
  • Women of childbearing potential must use method(s) of contraception; the individual methods of contraception should be determined in consultation with the treating physician or investigator
  • Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the administration of the investigational product; female patients who are not of childbearing potential as defined below, are eligible to be included (ie, meet at least one of the following criteria):
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy
  • Have medically confirmed ovarian failure; or
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women
  • Women must not be breastfeeding
  • Men who are sexually active with women of childbearing potential must use any contraceptive method with a failure rate of less than 1% per year
  • Contraception should be continued using two highly effective methods for a period of 90 days
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 40 mL/min (measured or calculated using the Cockcroft-Gault formula) using actual weight (ideal or adjusted weights are unacceptable)
  • White blood cells (WBC) >= 2000/uL
  • Neutrophils >= 1500/uL
  • Platelets >= 100x10^3/uL
  • Hemoglobin >= 9g/dL
  • Aspartate aminotransferase (AST) =< 3 x ULN
  • Alanine aminotransferase (ALT) =< 3 x ULN
  • Bilirubin =< 1.5 x ULN

Who cannot join

  • Patients with known symptomatic brain metastases requiring systemic corticosteroids; patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable; mild neurological deficit is allowed, if it does not interfere with the ability to judge the safety on the trial
  • Prior treatment with an mTOR inhibitor (including, but not limited to, everolimus, temsirolimus, sirolimus, and ridaforolimus)
  • Prior treatment with axitinib
  • History of or active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system
  • Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related illness
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug; inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
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  • Uncontrolled adrenal insufficiency
  • Any known active chronic liver disease
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
  • Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
  • Prior treatment with an anti-CD137, or OX40 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways except anti-PD1, anti-PDL1/2 antibodies or ipilimumab
  • Major surgery less than 6 weeks prior to the first dose of study drug; minor surgery less than 4 weeks prior to the first dose of study drug
  • Anti-cancer therapy less than 6 weeks prior to the first dose of study drug (less than 28 days for bevacizumab) or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug
  • Presence of toxicities attributed to prior therapy other than alopecia that have not resolved to grade 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4) or baseline before administration of study drug
  • History of grade 3 or higher immune-mediated adverse event (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune-modulatory therapy (e.g., checkpoint inhibitors, costimulatory agents etc.) or any grade immune-related adverse events (AEs) that required immune suppressive therapy
  • Patients with intolerance to or who have had a severe (>= grade 3) allergic or anaphylactic reaction to antibodies or infused therapeutic proteins, or patients who have had a severe allergic or anaphylactic reaction to any of the substances included in the investigational product (including excipients)
  • Patients with a previous history of adriamycin treatment and are at risk of cardiac failure (New York Heart Association [NYHA] class II or above)
  • Any one of the following currently or in the previous 6 months:
  • Myocardial infarction
  • Congenital long QT syndrome
  • Torsade's de points
  • Arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), and left anterior hemiblock (bifascicular block)
  • Unstable angina, coronary/peripheral artery bypass graft
  • Symptomatic congestive heart failure (congestive heart failure [CHF] New York Heart Association class III or IV)
  • Cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism or other clinical significant episode of thrombo-embolic disease (Cases must be discussed in detail with study chair to judge eligibility; anticoagulation (heparin only, no vitamin-K antagonists or factor Xa inhibitors) will be allowed if indicated)
  • Ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2, atrial fibrillation of any grade, or QT correction using Fridericia's correction formula (QTcF) interval > 470 msec at screening (except in case of right bundle branch block, these cases must be discussed with sponsor's medical monitor)
  • Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Concurrent use of any medications or substances; these include steroids as they may interfere with PF-04518600 (OX40 Ab); also strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole)
  • Presence of a malabsorption syndrome, gastrointestinal disorder, or gastrointestinal surgery that could affect the absorption of axitinib
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • Women who are pregnant or breastfeeding
  • Women with a positive pregnancy test
  • Prisoners or patients who are involuntarily detained

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22903

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Weill Cornell Medical College, New York- Presbyterian Hospital

    New York, New York, 10065

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase II Randomized Double Blind Trial of PF-04518600, an OX40 Antibody, in Combination With Axitinib Versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients With Metastatic Renal Cell Carcinoma

This randomized phase II trial studies how well axitinib with or without anti-OX40 antibody PF-04518600 work in treating patients with kidney cancer that has spread to other parts of the body. Biological therapies, such as anti-OX40 antibody PF-04518600, use substances made from living organisms that may may stimulate the immune system in different ways and stop tumor cells from growing. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving axitinib with or without anti-OX40 antibody PF-04518600 may work better in treating patients with kidney cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether a statistically significant improvement in progression free survival exists for patients receiving the combination.

SECONDARY OBJECTIVES:

  1. To determine whether the combination is safe and whether objective response rate (ORR), duration of response (DOR) and overall survival (OS) improve as a result of treatment with combination of axitinib + anti-OX40 antibody PF-04518600 (PF-04518600 [OX40 Ab]) compared to axitinib + placebo.

TERTIARY OBJECTIVES:

  1. To determine whether pre and post treatment specimens collected during the trial demonstrate significant changes in tumor microenvironment and enhanced immune response to tumor cells.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive axitinib orally (PO) twice daily (BID) on days 1-14 and anti-OX40 antibody PF-04518600 intravenously (IV) over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 90, and 180 days.

Being tested
Anti-OX40 Antibody PF-04518600, Axitinib, Laboratory Biomarker Analysis, Placebo
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-OX40 Antibody PF-04518600Biological

    Also called PF-04518600

    Given IV

  • AxitinibDrug

    Also called AG-013736, AG013736, Inlyta

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given IV

Study groups in NCT03092856
Study groupRoleWhat they receive
Arm I (axitinib, anti-OX40 antibody PF-04518600)ExperimentalPatients receive axitinib PO BID on days 1-14 and anti-OX40 antibody PF-04518600 IV over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Anti-OX40 Antibody PF-04518600; Drug: Axitinib; Other: Laboratory Biomarker Analysis
Arm II (axitinib, placebo)Active comparatorPatients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Axitinib; Other: Laboratory Biomarker Analysis; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    The statistical comparison of PFS in the two treatment arms will be based on the stratified logrank test.

    Measured: Time from randomization until the earliest of documented disease progression (confirmed progression of disease) or death, assessed for up to 180 days

Secondary outcomes (2)

  1. Incidence of unacceptable toxicity

    Defined as any toxicity or toxicities that necessitate the patient being removed from protocol therapy within the first 2 courses of therapy, or which cause a more than 6-week interruption of therapy or delay in starting a next course, up to the beginning of the 3rd therapy course.

    Measured: Up to the beginning of the third course (29 days)

  2. ORR defined as either complete response or partial response occurring any time during treatment and assessed by RECIST 1.1 and immune-related RECIST (irRECIST) criteria

    The two arms will also be compared using a one-sided 0.05-level Pearson chi-square test.

    Measured: Up to 180 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2017
  2. Study start19 Jul 2017
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03092856
Sponsor's protocol ID
4K-16-5
Other IDs
NCI-2017-00223, 4K-16-5, P30CA014089
Status last verified
May 2026
First submitted
22 Mar 2017
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-OX40 Antibody PF-04518600, Axitinib and Laboratory Biomarker Analysis in people with Clear Cell Renal Cell Carcinoma and Metastatic Renal Cell Cancer, run by University of Southern California at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Time from randomization until the earliest of documented disease progression (confirmed progression of disease) or death, assessed for up to 180 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03092856.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.

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