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

Calithera Biosciences

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer (NSCLC); Melanoma; Clear Cell Renal Cell Carcinoma (ccRCC)

Treatments: Drug: Nivolumab; Drug: CB-839

Study type: Interventional

Funder types: Industry

Identifiers

NCT02771626

CX-839-004

Details and patient eligibility

About

This study is an open-label Phase 1/2 evaluation of CB-839 in combination with nivolumab in participants with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.

Enrollment: 118 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

---

118 participants in 6 patient groups

Telaglenastat 600 mg + Standard Dose Nivolumab

Experimental group

Description:

Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic clear cell renal cell carcinoma (ccRCC), melanoma, and non-small cell lung cancer (NSCLC).

Treatment:

Drug: CB-839

Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors

Experimental group

Description:

Telaglenastat 800 mg/standard dose nivolumab combination in participants with advanced/metastatic ccRCC who have previously received at least one tyrosine kinase inhibitor (TKI) but are treatment naïve 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.

Treatment:

Drug: CB-839

Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab

Experimental group

Description:

Telaglenastat 800 mg/standard dose nivolumab combination in participants 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.

Treatment:

Drug: CB-839

Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy

Experimental group

Description:

Telaglenastat 800 mg/standard dose nivolumab combination in participants 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.

Treatment:

Drug: CB-839

Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy

Experimental group

Description:

Telaglenastat 800 mg/standard dose nivolumab combination in participants 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.

Treatment:

Drug: CB-839

Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy

Experimental group

Description:

Telaglenastat 800 mg/standard dose nivolumab combination in participants 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.

Treatment:

Drug: CB-839

Drug: Nivolumab