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)
Overview
- Phase
- Phase 2
- Intervention
- TG4010
- Conditions
- Non-Small-Cell Lung Carcinoma
- Sponsor
- Transgene
- Enrollment
- 222
- Locations
- 72
- Primary Endpoint
- Phase 3: Overall Survival (OS)
- Status
- Terminated
- Last Updated
- 9 years ago
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.
Investigators
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
- •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
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
Arms & Interventions
Arm 1 - TG4010 + first line therapy
First-line therapy and maintenance therapy
Intervention: TG4010
Arm 2 : Placebo + first line therapy
First-line therapy and maintenance therapy
Intervention: placebo
Outcomes
Primary Outcomes
Phase 3: Overall Survival (OS)
Time Frame: Approximately 27 months
OS is measured from date of randomization to date of death from any cause.
Phase 2: Progression-free Survival (PFS)
Time Frame: Approximately 15 months
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.
Secondary Outcomes
- 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 2: Safety(Approximately 15 months)
- Phase 3: Duration of response(Approximately 27 months)
- Phase 3 : Overall Response Rate (ORR)(Approximately 27 months)
- Phase 3: Safety(Approximately 27 months)
- Phase 2 : Duration of response(Approximately 15 months)