A Pilot Trial of Ipilimumab-Nivolumab in Local-Regionally Advanced Non Small Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 1
- Intervention
- Ipilimumab
- Conditions
- ALK Gene Rearrangement
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
This phase I trial studies the side effects of ipilimumab and nivolumab in combination with radiation therapy, and to see how well they work in treating patients with stage II-III non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Ipilimumab and nivolumab may also help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Giving ipilimumab and nivolumab in combination with radiation therapy may work better in treating patients with stage II-III non-small cell lung cancer compared to standard chemotherapy in combination with radiation therapy.
Detailed Description
PRIMARY OBJECTIVES: I. To determine safety and feasibility of ipilimumab-nivolumab (Bristol-Meyers-Squibb, Opdivo), a cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed death 1 (PD-1) inhibitor in the treatment of local-regionally advanced non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To evaluate the clinical outcomes of treatment with ipilimumab-nivolumab concurrent with radiation therapy in patients with local-regionally advanced NSCLC. II. To observe and record anti-tumor activity. III. To identify potential predictive and prognostic biomarkers for early recurrence using circulating cell-free deoxyribonucleic acid (DNA) (cfDNA). IV. To identify potential predictive and prognostic biomarkers for early recurrence using tumor tissue PD-L1 immunohistochemistry (IHC). V. To identify potential predictive and prognostic biomarkers for early recurrence using tumor tissue tumor mutational burden (TMB). VI. To identify potential resistance mechanisms using immune biomarker and genetic analysis in post-progression biopsies. EXPLORATORY OBJECTIVES: I. Tumor tissue/blood biomarkers will be assessed for tumor mutation burden (TMB) and PD-L1 immunohistochemistry. II. Patient microbiomes will be evaluated with stool specimen collection kits. OUTLINE: CONCURRENT THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 8 cycles, and treatment with ipilimumab repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 1 day of starting nivolumab and ipilimumab, patients also undergo radiation therapy 5 days a week (Monday-Friday) over 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed NSCLC (any histology)
- •Patients must have stage II or III local-regionally advanced NSCLC that is deemed to be best treated by systemic and concurrent radiotherapy. Eligible patients with stage II disease must be unresectable or refuse surgical resection
- •No prior therapy for the current stage II or stage III NSCLC disease
- •ECOG (Eastern Cooperative Oncology Group) performance status =\< 2 (Karnofsky \>= 60%)
- •Leukocytes \>= 2,000/mcL
- •Absolute neutrophil count \>= 1,000/mcL
- •Platelets \>= 75,000/mcL
- •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN
- •Creatinine =\< 1.5 x institutional ULN
Exclusion Criteria
- •Prior systemic therapy for the current active local-regionally advanced NSCLC
- •Patients who are receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because nivolumab is an immunotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab. These potential risks may also apply to radiation therapy used in this study
- •Known human immunodeficiency virus (HIV) positivity
- •Active chronic treatment (that is still required) with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents)
- •Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
Arms & Interventions
Treatment (nivolumab, ipilimumab, radiation therapy)
CONCURRENT THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 8 cycles, and treatment with ipilimumab repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 1 day of starting nivolumab and ipilimumab, patients also undergo radiation therapy 5 days a week (Monday-Friday) over 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Ipilimumab
Treatment (nivolumab, ipilimumab, radiation therapy)
CONCURRENT THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 8 cycles, and treatment with ipilimumab repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 1 day of starting nivolumab and ipilimumab, patients also undergo radiation therapy 5 days a week (Monday-Friday) over 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Nivolumab
Treatment (nivolumab, ipilimumab, radiation therapy)
CONCURRENT THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 21 days for up to 8 cycles, and treatment with ipilimumab repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 1 day of starting nivolumab and ipilimumab, patients also undergo radiation therapy 5 days a week (Monday-Friday) over 6-7 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Incidence of adverse events
Time Frame: Up to 2 years
Safety and tolerability will be assessed by the incidence and severity of adverse events as determined by Common Terminology Criteria for Adverse Events version 5 and by physical examination findings, clinical laboratory tests, and vital signs, assessments.
Secondary Outcomes
- Time to local treatment failure(Up to 2 years)
- Duration of response(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Anti-tumor activity(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)
- Time to distant treatment failure(Up to 2 years)
- Overall response rate(Up to 2 years)