Stage IV non small cell lung cancer (NSCLC) MedDRA version: 19.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864 MedDRA version: 19.0 Level: LLT Classification code 10025048 Term: Lung cancer non-small cell recurrent System Organ Class: 100000004864
Conditions
Interventions
Product Name: MVA-MUC1-IL2
Product Code: TG4010
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: mesmulogene ancovacivec
CAS Number: 1246525-59-6
Current Sponsor code: MVATG9931
Oth
Sponsors
Transgene S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female patients, age = 18 years old - Histologically confirmed NSCLC. NSCLC Not Otherwise Specified (NOS) are eligible except large cell neuroendocrine carcinoma. - Stage IV cancer according to TNM classification - Availability of histological material for Immunohistochemistry (IHC) staining on fixed paraffin embedded material; biopsy may come either from the primary tumor or from a metastasis - Patient's naïve to first-line therapy for the advanced stage of the disease. Previous neoadjuvant or adjuvant therapy or radiotherapy 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 computorized tomography scan or magnetic resonance imaging based on RECIST version 1.1 (CT is preferred for the chest exam) - Performance status 0 or 1 on the ECOG scale - Adequate hematological, hepatic, and renal function: * Hemoglobin = 10.0 g/dL * White Blood Cells = 3.0x1E+09/L including: Neutrophils = 1.5x1E+09/L Total lymphocytes count = 0.5x1E+09/L * Platelets count = 100x1E+09/L * Serum alkaline phosphatase =3 x upper limit of normal (ULN) in the absence of liver or bone metastases, and =5 ULN in patients with such metastases * Serum transaminases alanine aminotransferase and aspartate aminotransferase = 2.5 x ULN in the absence of liver metastases and = 5 x 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) - Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 309 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 191
Exclusion criteria
Exclusion criteria: - NSCLC with predominant squamous cell histology (mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is not eligible). Large cell neuroendocrine carcinoma are excluded - Patients having Central Nervous System (CNS) metastases (including leptomeningeal metastases). Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging and not treated by corticosteroids are allowed are allowed - EGFR activating mutations or ALK rearrangements leading to eligibility for TKI treatment (tests mandatory). Patients with documented ROS1-rearrangement (if already tested) are not eligible - 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 or Hepatitis C Virus; 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). However, prior surgery or radiation therapy aimed at local palliation or attempted local disease control is permitted within the 4 weeks before treatment start - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 10 mIU/mL) - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are: * women whose sexual orientation precludes intercourse with a male partner * women whose partners have been sterilized by vasectomy or other means * using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices [IUDs]; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable) - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase IIb part (completed): to prospectively validate the level of CD16+CD56+CD69+ lymphocytes, designed as TrPAL, as a predictive biomarker of TG4010's activity by comparing Progression-Free Survival (PFS) between the TG4010 arm (TG4010 + first-line therapy) and the placebo arm (placebo + first-line therapy) in the two subgroups of patients according to their level of TrPAL before randomization (normal and high level of TrPAL). Phase III part: To demonstrate that TG4010 improves overall survival (OS) as compared to placebo in stage IV NSCLC patients with non-squamous tumor histology receiving first-line chemotherapy: • in the whole study population • in the subgroup of patients with non-elevated TrPAL at baseline;Secondary Objective: Phase IIb part (completed): - Compare the 2 treatment arms with respect to OS, Overall Response Rate (ORR) and Time to Overall Response - Describe the Duration of Response (DoR) - Evaluate and to compare the safety profiles Phase III part: - To compare the 2 treatment arms with respect to the following endpoints repeated in the whole study population and in subgroups of patients with non-elevated TrPAL at baseline: PFS based on RECIST 1.1, 9-month PFS, ORR, and DoR - Quality of Life and pharmacoeconomic - Evaluate safety as assessed based on NCI-CTCAE in the whole study population, in patients with non-elevated TrPAL at baseline, and in patients with elevated TrPAL at baseline. - Compare PFS and OS in patients with elevated TrPAL at baseline Exploratory objectives of phase III: - Assess blood and cellular biomarkers or biomarker “profiles” with potential prognostic and/or predictive value on efficacy outcomes or biomarkers associated with TG4010 mechanism of action.;Primary end point(s): Phase IIb part (completed): PFS (time from the date of randomization to the date of first documented tumor progression or death due to any cause, whichever occurs first) Phase III part: OS (time from date of randomization to the d | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase IIb part (completed), secondary endpoints: - OS: defined in E.5.1 - ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST v.1.1 - Response rate at evaluation #2: proportion of patients having presented a CR or PR (even if not confirmed) at the 2nd tumor assessment after treatment start. - TOR: the start date is the date of randomization and the end date is the date of first documented response (CR or PR). - DoR: time from the date of first documented response (CR or PR) to the date of first documented disease progression or death due to underlying cancer - Safety: Incidence of AEs and SAEs assessed by the NCI CTCAE Phase IIb part (completed), exploratory endpoints: - Response rate at evaluation #2, change in tumor size over time: tumor size is defined as the sum of the longest diameters for all target lesions as identified at baseline - Efficacy and safety in subgroups of patients - Peripheral blood parameters: cellular and humoral response, immunophenotyping of lymphocytes, inflammatory and immune cytokines and related proteins, transcriptomics and genomics - Blood biomarkers with potential prognostic and/or predictive value on efficacy outcomes or biomarkers associated with TG4010 mechanism of action - Viral dissemination: skin swabs analyses by qPCR Phase III part, secondary endpoints: - PFS: defined in E.5.1 - ORR, DoR & safety: defined above - QoL: questionnaire QLQC30-LC13-EORTC - Pharmacoeconomic: Information obtained from the collection of medical care utilization data through eCRF may be combined with other data such as cost data or other clinical parameters Phase III part, exploratory endpoint: - Immune related biomarker evaluation;Timepoint(s) of evaluation of this end point: PFS & OS: see E.5.1.1 ORR & DoR: see E.5.1.1 TOR: 1st response or last tumor assessment Safety: evaluated throughout the study QoL: every 6 | — |
Countries
Australia, Belgium, Bulgaria, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, South Africa, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactTransgene Medical Affairs
Transgene S.A.
Outcome results
None listed