Homepage 2018-05-25T12:58:26+00:00

CB-839 in Combination with Cabozantinib

An investigational glutaminase inhibitor: the first of its class in the clinic

Genetic alterations in the metabolic pathways of tumors often cause a dramatic rise in the uptake of the nutrients glucose and glutamine. Removal of glutamine leads to a substantial reduction in cell growth or induces cell death in certain types of cancer cells, indicating that these cells are dependent on, or “addicted” to, glutamine.

The enzyme glutaminase, which converts glutamine to glutamate, has been identified as critical in the utilization of glutamine by cancer cells. CB-839 is designed to be a selective, reversible, and orally bioavailable inhibitor of human glutaminase.

In pre-clinical studies, CB-839 has been shown to be efficacious across a range of tumor types and has shown strong synergy with several kinase inhibitors that target growth factor pathways including cabozantinib. CB-839 has also been tested in combination with cabozantinib in a Phase 1 clinical trial, click here for more information.

Clinical Trial Schema

CANTATA is a global phase 2 randomized, double-blind, controlled study of CB-839 (a glutaminase inhibitor) in combination with cabozantinib (Cabometyx®) vs. placebo with cabozantinib, in patients with advanced or metastatic clear cell Renal Cell Carcinoma (RCC) (NCT03428217).

Eligibility Criteria

  • Documented histological or cytological diagnosis of RCC with a clear cell component
  • Age ≥ 18 years
  • Karnofsky Performance Status (KPS) ≥ 70%
  • Measurable disease per RECIST 1.1 as determined by the investigator
  • 1 or 2 prior systemic lines of therapy for advanced or metastatic RCC, including at least 1 anti-angiogenic therapy or the combination regimen of nivolumab + ipilimumab
    1. For the most recent anti-angiogenic therapy or nivolumab + ipilimumab, must have had radiographic progression of disease either during treatment or within 6 months following ≥ 4 weeks of treatment
    2. Must have had radiographic disease progression on the most recent systemic therapy within 6 months before randomization
    3. Prior treatment with other anticancer therapies including immunotherapy, cytokines, vaccines, monoclonal antibodies, and cytotoxic chemotherapy allowed
  • Prior treatment with cabozantinib (or other MET inhibitor) or CB-839
  • Central nervous system cancer, including brain metastases, unless treated and stable by symptoms and radiographic imaging for at least 4 weeks and not requiring steroids for 2 weeks before randomization
  • Unable to receive medications orally or presence of any condition that may prevent adequate absorption of oral study medication, including refractory nausea and vomiting, uncontrolled diarrhea, malabsorption, significant small bowel resection or gastric bypass surgery, and use of feeding tubes
  • Major surgery within 3 months prior to randomization
  • Complete wound healing from surgery is required 1 month prior to randomization
  • Uncontrolled, significant current or recent illness, including, but not limited to, the following conditions:
    • Cardiovascular disorders
      • Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias
      • Uncontrolled hypertension defined as sustained blood pressure > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment
      • Stroke (including transient ischemic attack), myocardial infarction, or other ischemic or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before randomization
    • Gastrointestinal (GI) disorders, including those associated with a high risk for perforation or fistula formation
      • Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction
      • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before randomization
    • Clinically significant hematuria, hematemesis, hemoptysis, or other history of significant bleeding within 3 months before randomization
    • Therapeutic anticoagulation with warfarin
      • Stable doses of therapeutic anticoagulation with other agents allowed
    • Lesions invading major pulmonary blood vessels
  • Requirement for continued proton pump inhibitor use after randomization

Study Objectives

Primary Objective

To assess the effect of CB-839 plus cabozantinib vs. cabozantinib plus placebo on Progression Free Survival (PFS) based on Independent Radiology Committee review per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Objectives

To assess the effect of CB-839 plus cabozantinib vs. cabozantinib plus placebo on Progression Free Survival (PFS) based on assessment by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

To assess the effect of CB-839 plus cabozantinib vs cabozantinib plus placebo on Overall Survival (OS)

Treatment Schedule

Treatment is double-blinded, placebo-controlled; all patients will take medications daily

Patients in the experimental arm (CB-839 plus cabozantinib) will take CB-839 orally twice daily and cabozantinib orally once daily

Patients in the comparator arm (placebo plus cabozantinib) will take placebo orally twice daily and cabozantinib orally once daily

Treatment will continue until unacceptable toxicity, disease progression, or study close

Study Locations

Locate a Study Location Near You

      Contact

      For more details about CANTATA or to refer patients:
      Call: 1-650-870-1028
      Visit: www.calithera.com
      Email: clinicaltrials@calithera.com

      If you have a clear cell renal cell carcinoma patient that has had 2 or more prior lines of therapy and is not eligible for CANTATA, click here to learn more about the ENTRATA Study: a randomized placebo controlled Phase 2 study of CB-839 in combination with everolimus (NCT03163667).

      This site is intended for US Healthcare Providers only.
      If you are a patient, please talk to your physician about this trial.