Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

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

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

Sponsors & Collaborators

• Calithera Biosciences, Inc

  lead INDUSTRY

Principal Investigators

• Samuel Whiting, MD, PhD · Calithera Biosciences, Inc

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-02-28

Primary Completion

2019-03-31

Completion

2019-03-31

Countries

• United States

Study Locations