Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)
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ClinicalTrials.gov Identifier: NCT02771626 |
Recruitment Status :
Completed
First Posted : May 13, 2016
Last Update Posted : August 19, 2021
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Condition or disease | Intervention/treatment | Phase |
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Clear Cell Renal Cell Carcinoma (ccRCC) Melanoma Non-small Cell Lung Cancer (NSCLC) | Drug: CB-839 Drug: Nivolumab | Phase 1 Phase 2 |
This study is an open-label Phase 1/ 2 evaluation of CB-839 in combination with nivolumab in patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.
During Phase 1, patients will be enrolled into escalating dose cohorts to determine the recommended phase 2 dose (RP2D).
In Phase 2, patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer will be enrolled into separate cohorts.
All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 118 participants |
Allocation: | Non-Randomized |
Intervention Model: | Factorial Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Glutaminase Inhibitor CB-839 in Combination With Nivolumab in Patients With Advanced/Metastatic Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer |
Study Start Date : | August 1, 2016 |
Actual Primary Completion Date : | April 24, 2020 |
Actual Study Completion Date : | April 24, 2020 |

Arm | Intervention/treatment |
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Experimental: CB-839 + Nivolumab Dose Escalation
Phase 1: CB-839 administered as oral capsules twice daily in combination with standard dose nivolumab in patients with advanced/metastatic ccRCC, MEL, and NSCLC to select the recommended Phase 2 dose (RP2D).
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Drug: CB-839
Glutaminase inhibitor
Other Name: telaglenastat Drug: Nivolumab PD-1 inhibitor
Other Names:
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Experimental: Clear Cell RCC Naïve to Checkpoint Inhibitors
Cohort 1: CB-839/nivolumab combination in patients with advanced/metastatic ccRCC who have previously received at least one tyrosine kinase inhibitors (TKI) but are treatment naive to checkpoint modulators programmed death-1/programmed death ligand-1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
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Drug: CB-839
Glutaminase inhibitor
Other Name: telaglenastat Drug: Nivolumab PD-1 inhibitor
Other Names:
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Experimental: Clear Cell RCC Recently Treated with Nivolumab
Cohort 2: CB-839/nivolumab combination in patients with advanced/metastatic ccRCC who received nivolumab in most recent treatment line that had documented radiological disease progression OR are currently receiving nivolumab with Stable Disease for at least 24 weeks.
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Drug: CB-839
Glutaminase inhibitor
Other Name: telaglenastat Drug: Nivolumab PD-1 inhibitor
Other Names:
|
Experimental: Clear Cell RCC with Prior PD-1 Therapy
Phase 2 - Cohort 3: CB-839/ nivolumab combination in patients with advanced/metastatic ccRCC that had documented radiological disease progression while receiving an anti-PD-1/PD-L1 therapy in any prior line of therapy.
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Drug: CB-839
Glutaminase inhibitor
Other Name: telaglenastat Drug: Nivolumab PD-1 inhibitor
Other Names:
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Experimental: Melanoma with Prior PD-1 Therapy
Cohort 4: CB-839/ nivolumab combination in patients with unresectable or metastatic melanoma that had documented radiological disease progression while receiving an anti-PD-1 therapy in their most recent line of therapy.
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Drug: CB-839
Glutaminase inhibitor
Other Name: telaglenastat Drug: Nivolumab PD-1 inhibitor
Other Names:
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Experimental: NSCLC with Prior PD-1 Therapy
Cohort 5: CB-839/ nivolumab combination with NSCLC that does not harbor an activating mutation in the epidermal growth factor receptor (EGFR) oncogene and who received nivolumab in most recent treatment line and had documented radiological disease progression OR are currently receiving nivolumab with Stable Disease for at least 24 weeks.
|
Drug: CB-839
Glutaminase inhibitor
Other Name: telaglenastat Drug: Nivolumab PD-1 inhibitor
Other Names:
|
- Safety and Tolerability of CB-839 and Nivolumab: Incidence of adverse events [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]
- Efficacy of CB-839 in Combination with Nivolumab: change in tumor size from baseline [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]
- Recommended Phase 2 Dose (RP2D) of CB-839 in Combination with Nivolumab [ Time Frame: 12 Weeks ]A minimum of 9-12 patients with ccRCC, melanoma, or NSCLC will be enrolled in Dose Escalation to determine RP2D.
- Maximum plasma concentration of CB-839 in combination with Nivolumab [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]Non-compartmental method of analysis will be used to analyze the plasma concentrations of CB-839.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Addition eligibility criteria based on tumor type apply
Inclusion Criteria:
- Ability to provide written informed consent in accordance with federal, local, and institutional guidelines
- Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- Life Expectancy of at least 3 months
- Adequate hepatic, renal, cardiac, and hematologic function
- Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria
- Resolution of treatment-related toxicities except alopecia
Exclusion Criteria:
- Unable to receive oral medications
- Unable to receive oral or intravenous (IV) hydration
- Intolerance to prior anti-PD-1/PD-L1 therapy
- Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)
- Any other current or previous malignancy within 3 years except protocol allowed malignancies
- Chemotherapy, TKI therapy, radiation therapy or hormonal therapy within 2 weeks
- Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: Some cohort exceptions allow anti-PD-1 therapy)
- Active known or suspected exclusionary autoimmune disease
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks
- History of known risks factors for bowel perforation
- Symptomatic ascites or pleural effusion
- Major surgery within 28 days before Cycle 1 Day 1
- Active infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks prior to first dose of study drug
- Patients who have human immunodeficiency virus (HIV), Hepatitis B or C
- Conditions that could interfere with treatment or protocol-related procedures
- Active and/or untreated central nervous system (CNS) disease or non-stable brain metastases

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02771626

Study Director: | Sam Whiting, MD, PhD | Calithera Biosciences, Inc |
Responsible Party: | Calithera Biosciences, Inc |
ClinicalTrials.gov Identifier: | NCT02771626 |
Other Study ID Numbers: |
CX-839-004 |
First Posted: | May 13, 2016 Key Record Dates |
Last Update Posted: | August 19, 2021 |
Last Verified: | August 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
RCC Melanoma (MEL) NSCLC Immuno-Oncology |
Tumor Metabolism Glutaminase Glutaminase Inhibitor |
Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Melanoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms |
Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nevi and Melanomas Adenocarcinoma Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Kidney Diseases Urologic Diseases Nivolumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors |