Early Switch Maintenance vs Delayed Second-line Nivolumab in Advanced Stage Squamous Non-small Cell Lung Cancer (NSCLC) Patients (EDEN Trial)

Study Overview
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Brief Summary
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The study's hypothesis is that using Nivolumab as early switch maintenance, after 4-6 cycles of standard first-line chemotherapy, might improve survival in patients with advanced stage squamous NSCLC.

Official Title
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An Open-label, Randomized Phase III Study of Early Switch Maintenance vs DElayed Second-line Nivolumab in Advanced Stage Squamous Non Small-cell Lung Cancer (NSCLC) Patients After Standard First-line Platinum-based Chemotherapy - EDEN Trial

Conditions
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Squamous Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Nivolumab 10 MG/ML Intravenous Solution
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathologically (histology or cytology) confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) histologically or cytologically confirmed stage IIIB-IV or recurrent squamous NSCLC with partial response (PR), complete response (CR) or stable disease (SD) according RECIST 1.1 after 4-6 courses of standard platinum-based chemotherapy (i.e. cisplatin or carboplatin combined with either paclitaxel, docetaxel, nab-paclitaxel, gemcitabine or vinorelbine) life expectancy ≥ 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status (PF) of 0-2 last chemotherapy course completed within 8 weeks before randomization and radiological assessment for tumor evaluation after first-line chemotherapy within 4 weeks before randomization in case of presence of treated brain metastases, lesions should be stable for at least 4 weeks, steroids should be off or on stable dose (≤ 10 mg of prednisone or equivalent), radiotherapy should have been completed at least 14 days before randomization and any Adverse Event (AE) related to radiotherapy recovered to grade < 1 (except alopecia) in case of females: postmenopausal status (at least 12 months after last menstrual period should have been passed) before the screening visit or surgical sterilization. Women of childbearing potential (WOCBP) must use 2 effective methods of contraception (from the time of informed consent signature trough 30 days after last trial drug dose) or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. Pregnancy should be avoided for 23 weeks after the last trial drug dose. WOCBP must have negative serum or urine pregnancy test within 24 hours prior to the start of trial drug treatment. in case of males: even if surgically sterilized, effective barrier contraception (method with failure rate < 1%/year) during the entire study treatment period and for a period of 31 weeks after the last dose of trial drug, or practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. laboratory parameters measured within 14 days prior randomization as follows: absolute neutrophil count ≥ 1000/mmc platelet count ≥ 75000/mmc haemoglobin ≥ 9g/dL total bilirubin ≤ 1.5x the Upper Normal Limit (local laboratory range) except in case of Gilbert Syndrome where total bilirubin value < 3.0 mg/dL is allowed serum alanine aminotransferase or aspartate aminotransferase or aspartate aminotransferase ≤ 3x the Upper Normal Limit (local laboratory range) creatinine ≤ 1.5x the Upper Normal Limit or estimated creatinine clearance using Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels above institutional limits stable medical conditions, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 4 weeks before randomization and otherwise noted in other eligibility criteria ability to comply with protocol requirements ability to provide written informed consent Exclusion Criteria: prior treatment with nivolumab or any other immunotherapy agent (e.g. anti-PD-1, anti-PD-L1, etc.) progressive disease after 4-6 cycles of first line platinum-based chemotherapy non-platinum-based first-line chemotherapy active, known or suspected autoimmune disease; please note: diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders, such as vitiligo, psoriasis or alopecia, not requiring systemic treatment, or conditions not expected to recur without external trigger are not excluded. condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior randomization; please note: topical, ocular, intranasal and inhalational corticosteroids with minimal systemic absorption, adrenal replacement steroid doses > 10 mg/day prednisone equivalent without concurrent autoimmune disease, brief course of corticosteroids treatment or prophylaxis or treatment of non-autoimmune conditions are allowed. patients with symptomatic and/or progressive brain metastases or with carcinomatous meningitis. previous malignancies unless complete remission has achieved at least 2 years prior to the study entry and no additional therapy is required or anticipated during the study period any medical condition, within 6 months before receiving the first dose of trial drug, considered relevant in the investigator's opinion. Please note: chronic stable atrial fibrillation on stable anticoagulant therapy are not excluded. Pacemaker may represent an exclusion criterion and should be discussed with the project clinician. Attention should be paid to the conditions requiring treatment with potentially hepatotoxic drugs considering the hepatotoxic potential of the trial drug. infection requiring an antibiotic therapy or other serious infection within 14 days before the first dose of trial drug positive serum pregnancy test, pregnancy or breast feeding condition (only for females) major surgery within 4 weeks (or 2 weeks for minor surgery) before study enrollment and not fully recovered to baseline or to a stable clinical status; lease note: insertion of vascular device is not excluded. interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity known history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired Immunodeficiency Syndrome (AIDS) any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection comorbidity or unresolved toxicities that would preclude administration of nivolumab.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, randomized in a 1:1 ratio to 2 treatment arms and stratified by centre and response to first-line induction therapy (minimization method)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A_Nivolumab<br>Nivolumab 240 mg IV every 2 weeks until disease progression, unacceptable toxicity, patient refusal or Investigator's decision | Drug: Nivolumab 10 MG/ML Intravenous Solution<br>* 240 mg as a 30 minutes IV infusion on Day 1 of each treatment cycle every 2 weeks, until intolerable toxicity or patient refusal or investigator's decision. In case of disease progression the treatment should be discontinued unless documented clinical benefits in the Investigator's judgement (no rapid progression, tolerance of trial drug, stable performance status, treatment maintenance does not delay an imminent intervention to prevent serious complication of PD) and no evidence of further progression at a radiographic assessment performed within 6 weeks. No dose escalations or reduction allowed. Administration delay until 6 weeks as well as resuming dose are allowed according to protocol defined criteria.<br>|
| Other: B_Best Supportive Care<br>Best Supportive Care until disease progression followed by Nivolumab at a dose of 240 mg IV until further disease progression, unacceptable toxicity, patient refusal or Investigator's decision. | Drug: Nivolumab 10 MG/ML Intravenous Solution<br>* 240 mg as a 30 minutes IV infusion on Day 1 of each treatment cycle every 2 weeks, until intolerable toxicity or patient refusal or investigator's decision. In case of disease progression the treatment should be discontinued unless documented clinical benefits in the Investigator's judgement (no rapid progression, tolerance of trial drug, stable performance status, treatment maintenance does not delay an imminent intervention to prevent serious complication of PD) and no evidence of further progression at a radiographic assessment performed within 6 weeks. No dose escalations or reduction allowed. Administration delay until 6 weeks as well as resuming dose are allowed according to protocol defined criteria.<br>Other: Best Supportive Care<br>* Care that aims to optimize the comfort, function and social support of the patients and their family at all stages of the illness. Best Supportive Care (BSC)includes the use of analgesics, antibiotics, blood tranfusions, blood products, radiotherapy, corticosteroids, antiemetics, antidiarrheals, vitamins and any intervention aiming the improvement of patient's discomfort. Any chemotherapy, immunotherapy and targeted therapy are not considered as part of BSC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Time from randomization to death date. Please note: a subject who has not died will be censored at the last known date alive. | From date of randomization until the date of death by any cause or study discontinuation due to lost to follow up/withdrawal of consent assessed up to 14 months . | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Time from randomization to the date of the first documented tumor progression (RECIST 1.1) or death due to any cause. Please note: clinical deterioration not radiologically confirmed is not considered progression for the purpose of this measure. Subjects who did not have any study tumor assessments and did not die will be censored on the date they were randomized. Subjects who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to the initiation od the subsequent anti-cancer therapy. | From date of randomization until the date of the first documented tumor progression or death by any cause, whichever occurs first, assessed up to 6 months in the arm B and 10 months in arm A. | 
| Progression-Free Survival from induction (PFSind) | Time from first chemotherapy cycle until documented tumor progression or death by any cause. | From date of first chemotherapy cycle until the date of the first documented tumor progression or death for any cause, whichever occurs first, assessed up to 10 months in the arm B and 14 months in arm A. | 
| Time to Treatment Failure (TTF) | Time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patients preference, Investigator's decision or death. | From date of randomization until the date of treatment discontinuation, assessed up to 9 months in the arm B and 14 months in arm A. | 
| Overall Survival from Induction (OSind) | Time from first chemotherapy cycle until death by any cause | From date of first chemotherapy cycle until the date of death, assessed assessed up to 14 months in the arm B and 18 months in arm A.. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous NSCLC, Nivolumab