Cabozantinib S-malate and Avelumab in Treating Participants with Metastatic Kidney Cancer

Status: Active


This phase I trial studies the side effects and best dose of cabozantinib s-malate and avelumab in treating participants with kidney cancer that has spread to other places in the body. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib s-malate and avelumab may work better in treating participants with metastatic kidney cancer.

Eligibility Criteria

Inclusion Criteria

  • Clinically, subject is a candidate for RCC diagnostic procedure (biopsy or surgery)
  • Subject meets standard of care eligibility criteria for consideration of treatment with immunotherapy using a checkpoint inhibitor following surgical resection
  • Histologically proven mRCC with a clear cell component
  • Radiographic evidence of metastatic disease
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Eastern Cooperative Oncology Group (ECOG) score 0-1
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL (may have been transfused)
  • Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN or AST and ALT levels =< 5 x ULN for subjects with documented metastatic disease to the liver; patient with history of unconjugated hyperbilirubinemia with otherwise acceptable liver enzyme levels (as per above criteria) may have higher bilirubin levels
  • Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  • Negative serum or urine pregnancy test at screening for women of childbearing potential
  • Highly effective contraception for both male and female subjects throughout the study and for at least 120 days after last avelumab treatment administration if the risk of conception exists
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria

  • Current use of immunosuppressive medication, except for the following: * Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) * Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent * Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent per treating physician’s clinical judgment; subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
  • Prior organ transplantation including allogenic stem-cell transplantation
  • Active infection requiring intravenous antibiotics (antibiotics should have been completed prior to registration)
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
  • Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. If the patient has a history of HBV or HCV then confirmatory PCR testing is required to confirm the disease is not active
  • Active and inactive vaccinations within 4 weeks of the first dose of avelumab and while on trial is prohibited
  • Prior exposure to checkpoint therapy OR cabozantinib
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.03 grade >= 3)
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 grade > 1); however, alopecia, sensory neuropathy grade =< 2, or other grade =< 2 not constituting a safety risk based on investigator’s judgment are acceptable
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment 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
  • Subjects taking prohibited medications; a washout period of prohibited medications for a period of at least two weeks or as clinically indicated should occur prior to the start of treatment
  • Pregnant women or lactating women who are breastfeeding are excluded from this study

Locations & Contacts


Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Neeraj Agarwal
Phone: 801-585-9682

Trial Objectives and Outline


I. To assess the safety and tolerability of avelumab + cabozantinib s-malate (Cabometyx) in subjects with metastatic renal cell carcinoma (mRCC) and determine the recommended phase II dose (RP2D).


I. To evaluate the clinical activity of avelumab + Cabometyx in subjects with mRCC.


I. To identify biomarkers (deoxyribonucleic acid [DNA], ribonucleic acid [RNA] or protein based) in tumor or in circulation that may predict response (progression-free survival [PFS], objective response rate) to of avelumab + Cabometyx in subjects with mRCC.

OUTLINE: This is a dose-escalation study of cabozantinib s-malate.

Participants receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28, and avelumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Participants who achieve clinical benefit may continue therapy for an additional year.

After completion of study treatment, participants are followed up every 6 months for 2 years following study enrollment.

Trial Phase & Type

Trial Phase

Phase I

Trial Type


Lead Organization

Lead Organization
Huntsman Cancer Institute / University of Utah

Principal Investigator
Neeraj Agarwal

Trial IDs

Primary ID HCI102309
Secondary IDs NCI-2018-00354 ID NCT03200587