E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIB-IV non small cell lung cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Advanced non small cell lung cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 100000015841 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the anti-tumor activity in terms of objective response rate (ORR) by using RECIST 1.1 in chemotherapy-naïve and immunotherapy-naïve advanced, non-squamous NSCLC patients with PD-L1 membrane staining on <50% of tumor cells receiving first-line chemotherapy (pemetrexed + carboplatin or cisplatin followed by pemetrexed maintenance therapy) plus TG4010 and nivolumab. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy with respect to: a) Progression Free Survival (PFS) b) Disease Control Rate (DCR) c) Overall Survival (OS) • To describe duration of response (DoR) • To evaluate the safety profile
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female or male patients age > 18 years-old • ECOG performance Status 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 or urine 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 post-treatment 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 |
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E.4 | Principal exclusion criteria |
• Patients having 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 co-stimulation or checkpoint pathways • Patients with EGFR activating mutations or ALK- rearrangements leading to eligibility for 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 HCV; presence in the serum of the antigens 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 any of the following cardiovascular conditions within 12 months of enrollment • Left ventricular ejection fraction less than the Lower Limit of Normal as assessed by echocardiography (or 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective Response Rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ORR: tumor assessment evaluated by RECIST 1.1 every 6 weeks from start of treatment until documented progression or for a period of 9 months after start of study treatment, whichever occurs first. Beyond 9 months of treatment, the evaluations will be performed every 12 weeks until documented progression |
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E.5.2 | Secondary end point(s) |
• Progression Free Survival (PFS) • Disease Control Rate (DCR) • Overall Survival (OS) • Duration of response (DoR) • Safety profile |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS, DCR, DoR: tumor assessment evaluated by RECIST 1.1 every 6 weeks from start of treatment until documented progression or for a period of 9 months after start of study treatment, whichever occurs first. Beyond 9 months of treatment, the evaluations will be performed every 12 weeks until documented progression
OS: after termination of study treatment, patients will be followed for survival on a 3-monthly basis
Safety: evaluated throughout the study
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
France |
Hungary |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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date of last patient inclusion + 18 months |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |