2018 GU CANCERS SYMPOSIUM: Early-Phase Trial of Glutaminase Inhibitor CB-839 in Combination With Cabozantinib or Everolimus in Renal Cell Carcinoma

Key Points

  • In patients treated with a combination of CB-839 and cabozantinib, 100% experienced tumor shrinkage and disease control; this includes four patients who had a partial response and eight patients who had stable disease.
  • In patients treated with a combination of CB-839 and everolimus, 92% experienced control of their disease, including 1 patient with a partial response and 21 patients with stable disease. 

Data on CB-839, a first-in-class glutaminase inhibitor, will be presented by Tannir et al at the 2018 Genitourinary Cancers Symposium in San Francisco (Abstract 603). The data are from the CX-839-001 study, which includes cohorts evaluating the safety, efficacy and recommended phase II dose of CB-839 in combination with everolimus (Afinitor) or cabozantinib (Cabometyx) in patients with metastatic renal cell carcinoma.

Combination With Cabozantinib

This is the first disclosure of clinical experience evaluating CB-839 in combination with cabozantinib, an oral receptor tyrosine kinase inhibitor. Preliminary results—to be presented on Saturday, February 10—show the combination demonstrated a 40% overall response rate in patients with advanced clear cell renal cell carcinoma and 100% disease control. The safety profile of CB-839 plus cabozantinib was generally consistent with that of cabozantinib monotherapy.  

As of December 22, 2017, 12 patients with advanced renal cell carcinoma were treated with CB-839 plus cabozantinib and evaluable for response, including 10 patients with clear cell disease and 2 with papillary disease. One hundred percent of evaluable patients experienced tumor shrinkage and disease control; this includes four patients who had a partial response and eight patients who had stable disease. In the clear cell patient population, the disease control rate was 100%, and the response rate was 40%.

Patients enrolled in the trial had advanced or metastatic disease and had received a median of three prior treatments, which included tyrosine kinase inhibitors, mTOR inhibitors, and checkpoint inhibitors. Patients were administered CB-839 in oral doses that ranged from 600 to 800 mg twice a day in combination with a fixed oral dose of cabozantinib at 60 mg once a day.

On the basis of these efficacy and safety data, which compares favorably to treatment with cabozantinib alone, Calithera plans to initiate the CANTATA trial, a randomized phase II placebo-controlled trial in approximately 300 patients with clear cell renal cell carcinoma who have previously received 1 or 2 prior lines of therapy. The CANTATA trial is expected to begin in the second quarter of 2018.

Combinaton With Everolimus

The updated results of CB-839 in combination with everolimus are also being presented. As of the data cutoff, patients with renal cell carcinoma with a median of three prior therapies were treated and evaluable for response. Ninety-two percent of patients experienced control of their disease, including 1 patient with a partial response and 21 patients with stable disease. 

The median progression-free survival was 5.8 months, which compares favorably to historical data in this patient population. On the basis of these efficacy and safety data, Calithera plans to continue development in combination with everolimus for the treatment of advanced clear cell renal cell carcinoma. The randomized phase II ENTRATA trial of CB-839 in combination with everolimus in patients with later-stage disease is currently enrolling and has been modified to enroll approximately 65 patients.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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