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Protocol No. EA5163

Principal Investigator Duma, Narjust

Phase III

Age Group Adult

Scope National

Sponsor Type National

Title INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature-Driven Analysis

Objective The purpose of this study is to compare any good and bad effects of using only the immunotherapy drug, MK-3475 (pembrolizumab), alone first versus the combination of the immunotherapy drug, MK-3475 (pembrolizumab), and chemotherapy. This study will also compare if adding chemotherapy to immunotherapy when the disease is growing is helpful. The addition of chemotherapy regimens to the usual immunotherapy could shrink your cancer or prevent it from returning. But, it could also cause side effects, which are described in the protocol

Group 1: MK-3475 for up to 2 years, if disease progression then carboplatin and pemetrexed for 4 doses then pemetrexed until disease progression
Group 2: MK-3475 for up to 2 years, If disease gets worse, then carboplatin and pemetrexed, and MK-3475. You will get up to 4 doses of carboplatin, but you will get both MK-3475 and pemetrexed for up to 2 years, until your disease gets worse or the side effects become too severe. After two years, you will get pemetrexed alone until your disease gets worse or the side effects become too severe
Group 3: MK-3475, and pemetrexed and carboplatin until your disease gets worse or the side effects become too severe. You will receive 4 doses of carboplatin while pemetrexed and MK-3475 (pembrolizumab) will be continue for up to 2 years total. If your disease gets worse sooner than 2 years, you will proceed to another therapy determined by your study doctor. If not, after 2 years, you will continue to get pemetrexed alone until your disease gets worse

Description A Randomized, Phase III Study of Firstline Immunotherapy alone or in Combination with Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non‐Small Cell Lung Cancer (NSCLC) with Immunobiomarker SIGNature‐driven Analysis

Key Eligibility
  • Must have histologically or cytologically confirmed stage IV non-squamous NSCLC (includes M1a, M1b, and M1c stage disease, AJCC 8th edition). Patients with Stage IIIB and IIIC disease are eligible if they are not candidates for combined chemotherapy and radiation
  • Must have PD-L1 expression Tumor Proportion Score (TPS) greater than or equal to 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed, the patients are not eligible. The assay must have been performed by a CLIA (or equivalent) certified laboratory
  • Must have measurable or non-measureable disease as defined by the protocol. The presence of malignant pleural fluid alone is sufficient to satisfy this eligibility criterion
  • Must be 18 years of age or older
  • ECOG Performance status 0-1
  • Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded
  • Treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. CNS progression counts as progression and patients must move on to the next phase after CNS treatment. Patients with asymptomatic new (at screening) or progressive brain metastases (active brain metastases at screening) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. Patients are eligible if off steroids for at least 14 days prior to protocol treatment. Palliative radiation to non-target lesions (bone metastasis) is allowed if patient develops symptoms. Anticonvulsants are allowed. Patients with asymptomatic, sub-centimeter brain metastasis who at the discretion of investigators do not need immediate CNS directed therapies are eligible
  • Must not have known pre-existing and clinically active interstitial lung disease, or a known history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
  • Must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, etc.)
  • Must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Must not have any other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
  • Can not be pregnant or breastfeeding, Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol
  • Must have adequate hematologic, liver and renal function as defined by the protocol
  • No known history of active tuberculosis (TB)
  • Must not have a diagnosis of immunodeficiency or receive systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol treatment
  • No prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC as defined by the protocol
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

  • Applicable Disease Sites Lung

    Status Open

    Participating Institutions Dean Health System, Hematology and Oncology Clinic ; Mercy Health Systems, Janesville ; Swedish American Hospital, Rockford ; UW Hospital and Clinics; UWCCC 1 South Park