A Study Evaluating the Efficacy and the Safety of First-line Chemotherapy Combined With the Therapeutic Vaccine Named TG4010 and Nivolumab in Patients With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is a multicenter, single arm, open label phase II study in treatment-naïve for advanced stage of the disease and immunotherapy-naïve patients with advanced non-squamous NSCLC and with < 50% of tumor cells expressing programmed death-ligand 1 (PD-L1) by immunohistochemical (IHC) staining.

Official Title
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A Phase II Study Evaluating the Efficacy and the Safety of First-line Chemotherapy Combined With TG4010 and Nivolumab in Patients With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non Small Cell Lung Cancer Metastatic

Intervention / Treatment
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* Biological: TG4010
* Drug: Chemotherapy
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Principal Inclusion Criteria: Female or male patients age > 18 years-old Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at study entry Life expectancy of at least 3 months Histologically confirmed non-squamous NSCLC (adenocarcinoma, large cell carcinoma, undifferentiated carcinoma or other) Stage IIIB-IV cancer or delayed relapse of any stage not amenable to surgery or radiotherapy with curative intent. PD-L1 expression by immunohistochemistry in < 50% of tumor cells Patients must be chemotherapy-naïve for the advanced stage of the disease. Previous neoadjuvant and/or adjuvant chemotherapy is allowed for patients who successfully underwent complete radical surgery and if last treatment was administered more than 12 months prior to the start of the study treatment. At least one measurable lesion by CT scan based on RECIST 1.1 performed within 28 days prior to start of study treatment Adequate hematological, hepatic, and renal functions Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug plus 30 days for a total of 5 months posttreatment completion. Highly effective contraception are defined in the protocol. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days for a total of 7 months post-treatment completion Principal Exclusion Criteria: Patients having central nervous system (CNS) metastases Patients with pericardial effusion Prior exposure to cancer immunotherapy including cancer vaccines, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-Lymphocyte antigen- 4 antibody or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways Patients with epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK)- rearrangements leading to eligibility for tyrosine kinase inhibitor (TKI) treatment (tests mandatory) Prior history of other malignancy except basal cell carcinoma of the skin, cervical intra epithelial neoplasia, and other cancer curatively treated with no evidence of disease for at least 3 years Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment Patients with an active, known or suspected autoimmune disease Patient with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity Patients with grade ≥ 2 neuropathy Signs or symptoms of infection within 14 days prior to start of study treatment or active infection requiring systemic therapy Positive serology for HIV or hepatitis C virus (HCV); presence in the serum of the antigens hepatitis B (HBs) at baseline Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g., elevated troponin or creatinine, uncontrolled diabetes) History of cardiovascular conditions within 12 months of enrollment Left ventricular ejection fraction less than the Lower Limit of Normal as assessed by echocardiography (or multigated acquisition (MUGA) scan) Patient with major surgery or radiotherapy within 3 weeks prior to the start of the study treatment. However, prior surgery or radiation therapy aimed at local palliation or attempted local disease control (except in case of thoracic radiotherapy) is permitted but has to be completed 2 weeks before treatment start Pregnant or nursing (lactating) women Patients with an organ allograft Any known allergy to eggs, gentamicin or history of allergy or hypersensitivity to study drug components Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatments

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TG4010/Chemotherapy/Nivolumab<br> | Biological: TG4010<br>* 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks<br>Drug: Chemotherapy<br>* Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance<br>Drug: Nivolumab<br>* 360 mg IV administration every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Percentage of participants whose best overall response is complete response or partial response using RECIST 1.1. confirmed by a second scan no less than 4 weeks after the criteria for response are first met. Complete response: disappearance of all lesions and no new lesions. Partial response: decrease of at least 30% in the sum of the diameters of measurable lesions taking as reference the baseline sum of diameters, no progression of non-measurable lesions and no new lesions. | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Time from the date of the first study drug administration to the date of first documented tumor progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Kaplan-Meier estimator was used to estimate median PFS and its confidence interval. | 28 months | 
| Disease Control Rate (DCR) | Percentage of participants whose best overall response is either complete response, partial response or stable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions and no measurable non-target lesions; Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD). | 15 months | 
| Overall Survival | Overall Survival (OS) is defined as the time from the first study drug administration to the date of death due to any cause. The Kaplan-Meier estimator was used to estimate median OS and its confidence interval. | 28 months | 
| Duration of Overall Response (DoR) | Time from first documented response (complete response or partial response) until documented disease progression or death due to lung cancer. | 28 months | 
| Number of Participants With Adverse Events or Abnormalities | The assessment of safety of the combination was based mainly on the frequency of adverse events, serious adverse events, adverse events of special interest (Injection site reaction, fatigue, pyrexia, infusion-related reactions and diarrhea), immune-mediated adverse events and laboratories abnormalities. | 28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic NSCLC, Advanced lung malignancy