NCT02071862

Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

Ph1 Study of the Safety, PK, and PDn of Escalating Oral Doses of the Glutaminase Inhibitor CB-839, as a Single Agent and in Combination With Standard Chemotherapy in Patients With Advanced and/or Treatment-Refractory Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 210 (actual)
• Sponsor: Calithera Biosciences, Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with solid tumors. This study is an open-label Phase 1 evaluation of CB-839 in patients with advanced solid tumors. The study will be conducted in 2 parts. Part 1 is a dose escalation study enrolling patients with locally-advanced, metastatic and/or refractory solid tumors to receive CB-839 capsules orally twice or three times daily. In Part 2, patients with each of the following diseases will be enrolled: A) Triple-Negative Breast Cancer, B) Non-Small Cell Lung Cancer (adenocarcinoma), C) Renal Cell Cancer, D) Mesothelioma, E) Fumarate hydratase (FH)-deficient tumors, F) Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST), G) SDH-deficient non-GIST tumors, H) tumors harboring mutations in isocitrate dehydrogenase-1 (IDH1) or IDH2, and I) cMyc mutation tumors. As an extension of Parts 1 \& 2, patients will be treated with CB-839 in combination with standard chemotherapy. Combination groups include: Pac-CB, CBE, CB-Erl, CBD, and CB-Cabo. Pac-CB: patients with locally-advanced or metastatic TNBC will be treated with paclitaxel and CB-839. CBE: patients with advanced clear cell RCC or papillary RCC will be treated with everolimus in combination with CB-839. CB-Erl: patients with advanced NSCLC lacking the T790M EGFR mutation will be treated with erlotinib and CB-839. CBD: patients with NSCLC harboring KRAS mutation will be treated with docetaxel and CB-839. CB-Cabo: patients with histologically confirmed diagnosis of locally-advanced, inoperable or metastatic RCC treated with cabozantinib in combination with CB-839. All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.

Conditions

• Solid Tumors
• Triple-Negative Breast Cancer
• Non Small Cell Lung Cancer
• Renal Cell Carcinoma
• Mesothelioma
• Fumarate Hydratase (FH)-Deficient Tumors
• Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST)
• Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors
• Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations
• Tumors Harboring Amplifications in the cMyc Gene

Interventions

Type	Name	Description
DRUG	CB-839	CB-839 monotherapy
DRUG	Pac-CB	CB-839 in combination with standard dose paclitaxel
DRUG	CBE	CB-839 in combination with standard dose everolimus
DRUG	CB-Erl	CB-839 in combination with standard dose erlotnib
DRUG	CBD	CB-839 in combination with standard dose docetaxel
DRUG	CB-Cabo	CB-839 in combination with standard dose cabozantinib

Timeline

• Start date: 2014-02-01
• Primary completion: 2019-03-01
• Completion: 2019-03-01
• First posted: 2014-02-26
• Last updated: 2022-07-20

Locations

13 sites across 1 country: United States