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Study CB-839 in Combination With Nivolumab in Patients With Melanoma, ccRCC and NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02771626
Recruitment Status : Active, not recruiting
First Posted : May 13, 2016
Last Update Posted : January 30, 2020
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Clear Cell Renal Cell Carcinoma Melanoma Non-small Cell Lung Cancer Drug: CB-839 Drug: Nivolumab Phase 1 Phase 2

Detailed Description:

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.

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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 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
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).
Drug: CB-839
Glutaminase inhibitor
Other Name: Glutaminase inhibitor

Drug: Nivolumab
PD-1 inhibitor
Other Names:
  • Opdivo
  • BMS-936558

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 TKI but are treatment naive to checkpoint modulators anti-PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
Drug: CB-839
Glutaminase inhibitor
Other Name: Glutaminase inhibitor

Drug: Nivolumab
PD-1 inhibitor
Other Names:
  • Opdivo
  • BMS-936558

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.
Drug: CB-839
Glutaminase inhibitor
Other Name: Glutaminase inhibitor

Drug: Nivolumab
PD-1 inhibitor
Other Names:
  • Opdivo
  • BMS-936558

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.
Drug: CB-839
Glutaminase inhibitor
Other Name: Glutaminase inhibitor

Drug: Nivolumab
PD-1 inhibitor
Other Names:
  • Opdivo
  • BMS-936558

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.
Drug: CB-839
Glutaminase inhibitor
Other Name: Glutaminase inhibitor

Drug: Nivolumab
PD-1 inhibitor
Other Names:
  • Opdivo
  • BMS-936558

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: Glutaminase inhibitor

Drug: Nivolumab
PD-1 inhibitor
Other Names:
  • Opdivo
  • BMS-936558




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 RECISTv1.1 criteria
  • Resolution of treatment-related toxicities except alopecia

Exclusion Criteria:

  • Unable to receive oral medications
  • Unable to receive oral or 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, Tyrosine Kinase Inhibitor 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 HIV, Hepatitis B or C
  • Conditions that could interfere with treatment or protocol-related procedures
  • Active and/or untreated CNS disease or non-stable brain metastases

Information from the National Library of Medicine

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


Locations
Show Show 17 study locations
Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
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Study Director: Sam Whiting, MD, PhD Calithera Biosciences, Inc

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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: January 30, 2020
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Calithera Biosciences, Inc:
RCC
MEL
NSCLC
Immuno-Oncology
Tumor Metabolism
Glutaminase
Glutaminase Inhibitor
Additional relevant MeSH terms:
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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