Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)

Sponsor

Calithera Biosciences, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT02771626

Collaborator

(none)

118

Enrollment

Locations

Arms

44.7

Duration (Months)

6.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 (ccRCC) Melanoma Non-small Cell Lung Cancer (NSCLC)	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.

Study Design

Study Type:

Interventional

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 :

Aug 1, 2016

Actual Primary Completion Date :

Apr 24, 2020

Actual Study Completion Date :

Apr 24, 2020

Arms and Interventions

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 Names: telaglenastat 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 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.	Drug: CB-839 Glutaminase inhibitor Other Names: telaglenastat 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 Names: telaglenastat 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 Names: telaglenastat 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 Names: telaglenastat 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 Names: telaglenastat Drug: Nivolumab PD-1 inhibitor Other Names: Opdivo BMS-936558

Outcome Measures

Primary Outcome Measures

Safety and Tolerability of CB-839 and Nivolumab: Incidence of adverse events [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 [Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months]

Secondary Outcome Measures

Recommended Phase 2 Dose (RP2D) of CB-839 in Combination with Nivolumab [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honor Health	Scottsdale	Arizona	United States	85016
2	Stanford University	Palo Alto	California	United States	94304
3	University of Colorado	Aurora	Colorado	United States	80045
4	University Cancer Blood Center	Athens	Georgia	United States	30607
5	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02114
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Karmanos Caner Center	Detroit	Michigan	United States	48201
9	New York University	New York	New York	United States	10016
10	Columbia University Medical Center	New York	New York	United States	10032
11	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10655
12	University Hospitals Cleveland	Cleveland	Ohio	United States	44106
13	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Vanderbilt University	Nashville	Tennessee	United States	37232
15	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
16	Seattle Cancer Care Alliance/University of Washington	Seattle	Washington	United States	98109
17	Northwest Medical Specialties	Tacoma	Washington	United States	98405