Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer

NCT03391869 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 2017-0311NCI-2018-00825
• Study Type: interventional
• Target: 339
• Locations: 1 country
• Sites: 5

Brief Summary

This phase III trial studies how well nivolumab and ipilimumab works with or without local consolidation therapy in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Local consolidation therapy, such as surgery or radiation therapy, may improve survival outcomes in patients with non-small cell lung cancer. It is not yet known whether giving nivolumab and ipilimumab with local consolidation therapy works better than nivolumab and ipilimumab alone in treating patients with stage IV non-small cell lung cancer.

Conditions

Lung Adenocarcinoma; Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS) in overall population

  The type I error of 0.10 for the entire study is divided in half (0.10/2 = 0.05) allowing for a Type I error of 0.05 for each of the efficacy endpoints.

  Up to 1 year after completion of study treatment

• OS in oligometastatic subgroup

  The assessment for the subpopulation of patients with oligometastatic disease will be conducted only if the finding in the total population is found to be non-significant. The type I error of 0.10 for the entire study is divided in half (0.10/2 = 0.05) allowing for a Type I error of 0.05 for each of the efficacy endpoints described above.

  Up to 1 year after completion of study treatment

Study Arms (2)

Arm A (ipilimumab, nivolumab)

EXPERIMENTAL

INDUCTION PHASE: Patients receive nivolumab IV over 90 minutes on days 1, 15, and 29, and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients receive nivolumab IV over 60 minutes on days 1, 15, and 29 and ipilimumab IV over 90 minutes on day 1. Courses repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab; Other: Quality-of-Life Assessment

Arm B (ipilimumab, nivolumab, LCT)

EXPERIMENTAL

INDUCTION PHASE: Patients receive nivolumab IV over 90 minutes on days 1, 15, and 29, and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients receive LCT consisting of surgery and/or radiation 14 days after completion of Induction Phase. Patients then receive nivolumab and ipilimumab as in arm A beginning within 4 weeks after LCT. Courses repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Procedure: Local Consolidation Therapy; Biological: Nivolumab; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Arm A (ipilimumab, nivolumab); Arm B (ipilimumab, nivolumab, LCT)

Local Consolidation Therapy PROCEDURE

Undergo radiation and/or surgery

Also known as: LCT, Local Consolidative Therapy

Arm B (ipilimumab, nivolumab, LCT)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (ipilimumab, nivolumab); Arm B (ipilimumab, nivolumab, LCT)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (ipilimumab, nivolumab); Arm B (ipilimumab, nivolumab, LCT)

Radiation Therapy RADIATION

Undergo radiation

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm B (ipilimumab, nivolumab, LCT)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Arm B (ipilimumab, nivolumab, LCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed non-small cell lung cancer; if a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer may be consented, but pathology must be confirmed prior to initiating treatment on study. Neuroendocrine carcinomas (e.g. small cell lung cancer \[SCLC\], carcinoid tumors) are not eligible. Carcinomas with neuroendocrine differentiation are eligible.
• Stage IV (according to the American Joint Committee on Cancer \[AJCC\] 8th edition) measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Signed and dated written or remote informed consent prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
• For lung adenocarcinoma patients, patients must not harbor any EGFR sensitizing or ALK fusion where there are standard care therapy options available. For patients with histologies other than adenocarcinoma, EGFR and ALK status is not required. Adenocarcinoma patients may be consented prior to the EGFR and ALK status being known, but EGFR and ALK status must be determined prior to initiating therapy. EGFR and ALK status may be determined using either tumor- or plasma-based, Clinical Laboratory Improvement Amendments (CLIA)-certified assays. For patients with non-small cell lung cancer (NSCLC), not otherwise specified (NOS), EGFR/ALK testing is not required, as the frequency of alterations is exceedingly rare in this histology. Also, note that patients with ROS1/RET alterations can be enrolled, as tyrosine kinase inhibitor such as crizotinib aren't established as first line therapy for patients with these alterations.
• One prior line of chemotherapy and/or targeted agents for metastatic disease are permitted. This chemotherapy can include maintenance therapy, as long as it was given in the front line setting. In addition, prior antiangiogenic therapy (e.g. bevacizumab) is permitted if used as frontline treatment.
• Patients must have organ and marrow function as defined below:
• Performance status of 0 or 1 if using Eastern Cooperative Oncology Group (ECOG)/Zubrod.
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to treatment initiation
• White blood cell (WBC ) \>= 2000/uL
• Neutrophils \>= 1500/uL (obtained within 14 days prior to randomization/registration)
• Platelets \>= 100 x 10\^3/uL (obtained within 14 days prior to randomization/registration)
• Hemoglobin \> 9.0 g/dL (obtained within 14 days prior to randomization/registration)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL (if using the Cockcroft-Gault formula)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN (obtained within 14 days prior to randomization/registration)
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL) (obtained within 14 days prior to randomization/registration)

You may not qualify if:

• Systemic immunotherapy for metastatic NSCLC. Immunotherapy agents include, but are not limited to, agents targeting the PD1/PD-L1 axis (e.g. nivolumab, pembrolizumab, atezolizumab, durvalumab) or CTLA-4 (ipilimumab, tremelimumab) pathways.
• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to the initiation of study treatment. The following exceptions are allowed: hormone-replacement therapy or oral contraceptives
• Women must not be breastfeeding.
• Patients excluded with any prior treatment of pneumonitis requiring corticosteroids within 60 days prior to the first dose of nivolumab
• Unwillingness or inability to follow the procedures required in the protocol.
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Prior malignancy active within the previous 2 years. Patients with locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation) are eligible.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration (i.e. disease-modifying antirheumatic drugs). Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Note that subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \>10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution.
• Patients should be excluded if they are known to be positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• History of allergy to study drug components.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Prisoners or subjects who are involuntarily incarcerated.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (5)

MD Anderson in The Woodlands

Conroe, Texas, 77384, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MD Anderson West Houston

Houston, Texas, 77079, United States

Location

MD Anderson League City

League City, Texas, 77573, United States

Location

MD Anderson in Sugar Land

Sugar Land, Texas, 77478, United States

Location

Related Publications (2)

• Altan M, Li R, Li Z, Chen R, Sheshadri A, Tran HT, Little L, Baguley J, Sinson J, Vokes N, Gandhi S, Antonoff MB, Swisher SG, Lizee G, Reuben A, Heymach JV, Zhang J. High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC. J Immunother Cancer. 2024 Dec 25;12(12):e008950. doi: 10.1136/jitc-2024-008950.

  PMID: 39721752 DERIVED

• Altan M, Li QZ, Wang Q, Vokes NI, Sheshadri A, Gao J, Zhu C, Tran HT, Gandhi S, Antonoff MB, Swisher S, Wang J, Byers LA, Abdel-Wahab N, Franco-Vega MC, Wang Y, Lee JJ, Zhang J, Heymach JV. Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events. Front Immunol. 2023 Dec 12;14:1322818. doi: 10.3389/fimmu.2023.1322818. eCollection 2023.

  PMID: 38152395 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Therapeutics; Physical Phenomena

Study Officials

• John V Heymach, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 5, 2018
• Study Start: December 29, 2017
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

US (5)