Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Carcinoma, Renal Cell

Gastrointestinal Stromal Tumors

Hematoma, Subdural

Mesothelioma

Mesothelioma, Malignant

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Breast Diseases

Skin Diseases

Adenoma

Neoplasms, Mesothelial

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Paclitaxel

Docetaxel

Everolimus

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Glutamine

CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose paclitaxel in 28-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose everolimus in 28-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose erlotnib in 28-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose docetaxel in 21-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose cabozantinib in 28-day cycles until disease progression or unacceptable toxicity

CB-839

CB-839 in combination with standard dose paclitaxel

Pac-CB

CB-839 in combination with standard dose everolimus

CB-839 in combination with standard dose erlotnib

CB-Erl

CB-839 in combination with standard dose docetaxel

CB-839 in combination with standard dose cabozantinib

CB-Cabo

Samuel Whiting, MD, PhD

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.

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

Calithera Biosciences, Inc

Spots Global Cancer Trial Database for tumors harboring amplifications in the cmyc gene