Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This is a Phase IIb/III randomized, double-blind, placebo-controlled study to compare the efficacy and safety of first-line therapy combined with TG4010 or placebo in stage IV non-small cell lung cancer (NSCLC). TG4010 is a suspension of recombinant Modified Vaccinia virus strain Ankara (MVA strain) carrying coding sequences for human MUC1 antigen and human interleukin-2 (IL2). TG4010 has been developed for use as an immunotherapy in cancer patients whose tumors express the MUC1 antigen. TG4010 is intended to induce a MUC1-specific cellular immune response and to produce a non-specific activation of several components of the immune system.

Official Title
-----------------
A Phase IIB/III Randomized, Double-blind, Placebo Controlled Study Comparing First Line Therapy With or Without TG4010 Immunotherapy Product in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

Conditions
-----------------
Non-Small-Cell Lung Carcinoma

Intervention / Treatment
-----------------
* Biological: TG4010
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other) Stage IV cancer according to TNM classification (7th edition - UICC, December 2009; includes tumor with malignant pleural or pericardial effusion Tumor biopsy specimen with ≥ 50% of MUC1 expressing tumor cells determined by Immunohistochemistry (IHC) staining on fixed pathological material. Biopsy may come either from the primary tumor or from a metastasis. Cytological material is not accepted for this analysis Patient's naïve to first-line therapy for the advanced stage of the disease. Previous neoadjuvant or adjuvant therapy 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, i.e., D1 of Cycle 1. At least one measurable lesion by CT scan or MRI based on RECIST version 1.1 PS 0 or 1 on the ECOG scale Adequate hematological, hepatic, and renal function: Hemoglobin ≥ 10.0 g/dL White Blood Cells (WBC) ≥ 3.0x10E9/L including Neutrophils ≥ 1.5x109/L Total lymphocytes count ≥ 0.5x10E9/L Platelets count ≥ 100x10E9/L Serum alkaline phosphatase ≤ 3x ULN (upper limit of normal)in the absence of liver or bone metastases or ≤5 ULN(in patients with documented bone or liver metastases) Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) ≤ 2.5 x ULN in the absence of liver metastases or =< 5 ULN in case of liver metastases) Total bilirubin ≤1.5 x ULN Glomerular Filtration Rate ≥ 60 mL/min (according to Modification of the Diet in Renal Disease (MDRD) formula or cockroft & Gault formula) Serum albumin ≥ 30 g/L Effective contraception during the study period and for 3 months after the last study treatment administration (male and female patient) Exclusion Criteria: Patients having Central Nervous System (CNS) metastases. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed Documented EGFR activating mutations (if already tested) Prior history of other malignancy except: Basal cell carcinoma of the skin Cervical intra epithelial neoplasia Other cancer curatively treated with no evidence of disease for at least 5 years Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (e.g., cyclosporine) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to the start of the study treatment (i.e., D1 of Cycle 1) Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV); presence in the serum of the antigens HBs 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) Patient with major surgery or radiotherapy within 4 weeks prior to the start of the study treatment (i.e., D1 of Cycle 1). Prior surgery or radiation therapy aimed at local palliation or attempted local disease control is permitted Patient with an organ allograft Known allergy to eggs, gentamicin or platinum-containing compounds Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment (i.e., D1 of Cycle 1) Patient unable or unwilling to comply with the protocol requirements Pregnancy or lactation Bevacizumab will be allowed for patients with non-squamous carcinoma. Prescribing information must be followed and precautions have to be taken into consideration (e.g., patients having presented a serious hemorrhage or recent hemoptysis should not receive bevacizumab).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - TG4010 + first line therapy<br>First-line therapy and maintenance therapy | Biological: TG4010<br>* TG4010 • TG4010 will be administered starting on Day 1 (D1) of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by subcutaneous (SC) injections and then once every 3 weeks until progression or discontinuation due to any reason. Chemotherapy (and bevacizumab if prescribed), will be given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles. First line therapy: Non-squamous carcinoma: pemetrexed + cisplatin or paclitaxel + carboplatin +/- bevacizumab Squamous carcinoma: gemcitabine + cisplatin or paclitaxel + carboplatin Maintenance therapy: • Pemetrexed or erlotinib for eligible patients and according to labeling.<br>|
| Active Comparator: Arm 2 : Placebo + first line therapy<br>First-line therapy and maintenance therapy | Drug: placebo<br>* Placebo will be administered starting on D1 of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by SC injections and then once every 3 weeks until progression or discontinuation due to any reason. First line therapy: as in Arm 1 Maintenance therapy: as in Arm 1<br>* Other names: erlotinib;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Progression-free Survival (PFS) | PFS is measured from date of randomization to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment. | Approximately 15 months | 
| Phase 3: Overall Survival (OS) | OS is measured from date of randomization to date of death from any cause. | Approximately 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 : Overall Survival (OS) |  | Approximately 15 months | 
| Phase 2 : Overall Response Rate (ORR) |  | Approximately 15 months | 
| Phase 3: Progression-free Survival (PFS) |  | Approximately 27 months | 
| Phase 3 : Overall Response Rate (ORR) |  | Approximately 27 months | 
| Phase 2 : Duration of response |  | Approximately 15 months | 
| Phase 2: Safety |  | Approximately 15 months | 
| Phase 3: Duration of response |  | Approximately 27 months | 
| Phase 3: Safety |  | Approximately 27 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NSCLC