A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment

Not Recruiting

Trial ID: NCT04338269


This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.

Official Title

A Phase III, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination With Cabozantinib Versus Cabozantinib Alone in Patients With Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma Who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment

Stanford Investigator(s)

Sandy Srinivas
Sandy Srinivas

Professor of Medicine (Oncology) and, by courtesy, of Urology


Inclusion Criteria:

   - Histologically confirmed locally advanced or metastatic clear cell or non-clear cell
   (papillary, chromophobe, and unclassified only) RCC. RCC with sarcomatoid features is
   allowed. Patients with the chromophobe subtype of non-clear cell RCC must have
   sarcomatoid differentiation.

   - Radiographic disease progression to prior ICI therapy for RCC. Patients who
   experienced radiographic tumor progression during or within 6 months after the last
   dose of adjuvant ICI are also eligible. ICI is defined by anti-PD-L1 or anti-PD1
   antibody including atezolizumab, avelumab, pembrolizumab, durvalumab, or nivolumab.
   Only patients for whom the immediate preceding line of therapy was an ICI are allowed.

   - Measurable disease per RECIST v1.1

   - Evaluable IMDC risk score

   - Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening,
   if clinically feasible. Both archival and fresh samples are preferred.

   - KPS score of >=70

   - Recovery to baseline or Grade    prior treatments, unless adverse events are clinically nonsignificant and/or stable in
   the opinion of the investigator. Grade 2 alopecia is allowed for study participation

   - Adequate hematologic and end-organ function

   - Negative HIV test at screening

   - Negative hepatitis B testing at screening

   - Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
   test followed by a negative HCV RNA test at screening

   - For women of childbearing potential: agreement to remain abstinent (refrain from
   heterosexual intercourse) or use contraception and agreement to refrain from donating

   - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
   a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

   - Treatment with anti-cancer therapy within 14 days prior to initiation of study

   - Patients received cabozantinib at any time prior to screening

   - Patients who received more than one ICI treatment in the locally advanced or
   metastatic setting

   - Patients who received more than two prior lines of therapy in the locally advanced or
   metastatic setting

   - Patients who have received a mammalian target of rapamycin (mTOR) inhibitor in any

   - Symptomatic, untreated, or actively progressing CNS metastases

   - History of leptomeningeal disease

   - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
   drainage procedures

   - Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring
   continued use of bisphosphonate therapy or denosumab

   - History of malignancy other than renal carcinoma within 5 years prior to screening,
   with the exception of malignancies with a negligible risk of metastasis or death

   - Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1

   - Active tuberculosis

   - Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation
   of study treatment, or anticipation of need for a major surgical procedure during the

   - Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
   or within 5 months after final dose of atezolizumab and 4 months after final dose of

   - Severe infection within 4 weeks prior to initiation of study treatment, including, but
   not limited to, hospitalization for complications of infection, bacteremia, or severe
   pneumonia, or any active infection that, in the opinion of the investigator, could
   impact patient safety

   - Pharmacologically uncompensated, symptomatic hypothyroidism

   - Uncontrolled hypertension defined as sustained blood pressure >150 mm Hg systolic or >
   90 mm Hg diastolic despite optimal antihypertensive treatment (all countries except
   France); sustained BP > 140 mmHg systolic or > 90 mmHg diastolic despite optimal
   antihypertensive treatment (France only)

   - Significant cardiovascular disease (such as New York Heart Association Class II or
   greater cardiac disease, unstable arrhythmia, or unstable angina) within 3 months
   prior to initiation of study treatment

   - Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring
   surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day
   1 of Cycle 1

   - History of congenital QT syndrome

   - History or presence of an abnormal ECG that is clinically significant in the
   investigator's opinion

   - Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin
   inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors
   (e.g. clopidogrel)


drug: Atezolizumab

drug: Cabozantinib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Denise Haas

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