Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer

Running, not enrolling · Phase 2

Conditions studied: Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8

In brief

This phase II trial compares cabozantinib alone and the combination of cabozantinib and nivolumab to standard chemotherapy in the treatment of patients with non-squamous non-small cell lung cancer (NSCLC). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ramucirumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as docetaxel, gemcitabine hydrochloride, paclitaxel, and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cabozantinib alone or in combination with nivolumab may be more effective than standard chemotherapy in treating patients with non-small cell lung cancer.

Key facts

Study ID

NCT04310007

Run by

National Cancer Institute (NCI)

People needed

117

Starts

2020-07-13

Expected to finish

2026-12-31

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• RANDOMIZATION (STEP 1): Patient must be >= 18 years of age
• RANDOMIZATION (STEP 1): Patient must have pathologically confirmed non-squamous non-small cell lung carcinoma (NSCLC). Patients with NSCLC not otherwise specified (NOS) are eligible. Mixed tumors will be categorized by predominant cell type. If small cell elements are present, the patient is ineligible
• RANDOMIZATION (STEP 1): Patient must have metastatic stage IVA or IVB disease (includes M1a, M1b, and M1c), according to the 8th edition of the lung cancer TNM classification system. Recurrent metastatic NSCLC ineligible for curative therapy (in the treating investigator's opinion) is also allowed
• RANDOMIZATION (STEP 1): Patient's tumor must be known negative for EGFR tyrosine kinase inhibitor (TKI) sensitizing mutations (for example at a minimum, negative for EGFR Exon 19 deletions, EGFR exon 20 insertions, and Exon 21 L858R, L861Q mutations ) AND negative for ALK gene rearrangements (by fluorescence in situ hybridization [FISH], next generation sequencing [NGS], or immunohistochemistry [IHC]) by routine Clinical Laboratory Improvement Amendments (CLIA)- or Food and Drug Administration (FDA)-certified clinical testing methods. CLIA or FDA approved circulating tumor deoxyribonucleic acid (DNA) testing is acceptable as an alternative to tissue testing
• RANDOMIZATION (STEP 1): Patient must have radiographic and/or clinical progression (per local investigator assessment) following one, but only one, line of platinum-based chemotherapy AND one, but only one, line of prior checkpoint inhibitor (anti-PD-1 or PD-L1) immunotherapy, either concurrently or sequentially in either order. A minimum of two doses of prior immunotherapy is required. Only one prior line of therapy is allowed if patients received chemotherapy and immunotherapy together (patients may not receive subsequent single agent chemotherapy), and greater than two prior lines of therapy are not allowed.
• NOTE: Lines of therapy are defined by clinical or radiographic progression. For patients with recurrent metastatic NSCLC following treatment for stage 1-3 NSCLC, platinum-based chemotherapy received within 12 months of recurrence and/or immunotherapy received within 6 months of recurrence will meet the requirement for prior chemotherapy and/or immunotherapy but subsequent receipt of more immunotherapy and/or platinum-based chemotherapy is also allowed.
• NOTE: Prior anti-VEGF antibody therapy (ie bevacizumab) is allowed. Prior ipilimumab, or investigational agents not excluded below, in combination with the required prior therapies above are allowed.
• NOTE: Prior receipt of one or two lines of targeted therapy for ROS1, RET, MET, BRAF, ERBB2/HER2, or KRAS G12C positive NSCLC is allowed and will not count toward the line of therapy limit. However, progression is still required after chemotherapy and immunotherapy as above. Patients with ROS1, RET, MET positive NSCLC are strongly encouraged to get appropriate targeted therapy (such as crizotinib, entrectinib, lorlatinib, selpercatinib, pralsetinib, capmatinib, tepotinib, or another investigational, off-label, or approved agent directed against ROS1, RET, or MET positive NSCLC) prior to participation and will be stratified.
• NOTE: No prior predominantly VEGFR directed TKI therapy (such as cabozantinib, lenvatinib, or sitravantinib) is allowed, except for the agents named above.
• RANDOMIZATION (STEP 1): The investigator must document the intended chemotherapy regimen should their patient be randomized to Arm C (docetaxel and ramucirumab, OR single agent chemotherapy - docetaxel, gemcitabine, paclitaxel, nab-paclitaxel). The patient must not have received the selected chemotherapy agent previously for metastatic disease
• RANDOMIZATION (STEP 1): Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the following times prior to randomization:
• FDA approved targeted oral therapy must be completed >= 1 week prior
• Chemotherapy and/or immunotherapy must be completed >= 2 weeks prior
• Prior investigational agents must be completed >= 4 weeks prior.
• RANDOMIZATION (STEP 1): Prior radiation therapy is allowed with a 2 week washout prior to randomization. Patient must not receive any systemic treatment with radionuclides within 6 weeks prior to randomization. Patient must have no clinically relevant ongoing complication from prior radiation therapy
• RANDOMIZATION (STEP 1): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (in the opinion of the treating physician) are eligible for this trial
• RANDOMIZATION (STEP 1): Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents (such as anthracycline or HER2-directed antibody therapy, but not prior checkpoint inhibitor therapy), must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
• RANDOMIZATION (STEP 1): Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Patient must have met the eligibility criteria outlined above
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Patient must have measurable disease as defined by RECIST v1.1. Measurements must be obtained within 4 weeks prior to randomization/registration
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Patient must have recovered to equal to or less than grade 1 toxicities related to prior treatment, unless toxicities are clinically non significant and/or stable on supportive therapy (as determined by the treating physician)
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Absolute neutrophil count >= 1,500/mcL (obtained within 2 weeks prior to randomization)
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Platelets >= 100,000/mcL (obtained within 2 weeks prior to randomization)
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Hemoglobin >= 9 g/dL (obtained within 2 weeks prior to randomization)
• RANDOMIZATION (STEP 1 - ALL TREATMENT ARMS): Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (for patients with Gilbert's disease total bilirubin must be =< 3 x ULN) (obtained within 2 weeks prior to randomization)

Where it is running

• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center — Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States
• CTCA at Western Regional Medical Center — Goodyear, Arizona, United States
• Kingman Regional Medical Center — Kingman, Arizona, United States
• Cancer Center at Saint Joseph's — Phoenix, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs — Hot Springs, Arkansas, United States
• Mission Hope Medical Oncology - Arroyo Grande — Arroyo Grande, California, United States
• PCR Oncology — Arroyo Grande, California, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Mercy Cancer Center - Carmichael — Carmichael, California, United States
• Mercy San Juan Medical Center — Carmichael, California, United States
• Mercy Cancer Center - Elk Grove — Elk Grove, California, United States
• Washington Health — Fremont, California, United States
• Fremont - Rideout Cancer Center — Marysville, California, United States
• Veterans Administration Medical Center - Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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