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Clinical Trial 20614

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT04338269

Phase: Phase III
Prinicipal Investigator: Jad Chahoud

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Overview

Study Title

A Phase III, Multicneter, 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

Summary

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.

Objective

This study will evaluate the efficacy and safety of atezolizumab when given in combination with cabozantinib (Atezo; Cabo) compared with cabozantinib alone in patients with advanced clear cell or non;clear cell RCC (papillary or unclassified only) who experienced radiographic tumor progression during or after ICI treatment in the metastatic setting.

Treatments

Therapies

Medications

Atezolizumab (Tecentriq); Cabozantinib (XL 184)

Inclusion Criteria

Inclusion Criteria:

  • Histologically confirmed locally advanced or metastatic clear cell or non-clear cell (papillary and chromophobe unclassified only) RCC. RCC with sarcomatoid features is allowed.
  • Radiographic disease progression to prior ICI therapy for RCC ICI for metastatic disease: Radiographic disease progression during or following ICI treatment for locally advanced or metastatic RCC either in first- or second-line treatment. ICI for adjuvant therapy: Patients who experienced radiographic tumor progression during or within 6 months after last dose of adjuvant ICI are also eligible. Examples of ICI regimens include one ICI regiment in first-line treatment (e.g., nivolumab plus ipilimumab, pembrolizumab plus axitinib, axitinib plus avelumab) or second line treatment (e.g., TKI as first line treatment and ICI as second-line treatment) ICI is defined by anti-PD-L1 or anti-PD1 antibody, including atezolizumab, avelumab, pembrolizumab, durvalumab, or nivolumab. Ipilimumab monotherapy is not considered an anti-PD-L1 or anti-PD1 therapy. Patients must have received at least 2 cycles of ICI treatment. ICI must have been used in the immediate preceding line of therapy. (Patients with an intervening treatment between ICI and study screening are excluded) Adjuvant treatment with VEGFR-TK1s, except cabozantinib, is allowed
  • Measurable disease per RECIST v1.1
  • Evaluable IMDC risk scores
  • Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible
  • KPS score of >=70
  • Recovery to baseline of grade 1 or less NCI CTAE v5.0 from toxicities related to any 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 eggs
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

  • Exclusion Criteria

    Exclusion Criteria:

  • Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
  • Patients who 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 setting
  • 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 study
  • 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 cabozantinib
  • 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.
  • Uncontrolled hypertension defined as sustained blood pressure >150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, MI, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Significant vascular disease (e.g., aortic aneurysm 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)
  • Other exclusions apply

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