| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-Small-Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It usually grows and spreads more slowly than small cell lung cancer. |
|
| 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 | 10029514 |
| E.1.2 | Term | Non-small cell lung cancer NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
Step 1 (phase II) 2:1 randomized non-comparative one stage Fleming phase II
Primary objective
To evaluate the overall survival (OS) rate at 12 months in HLA-A2 positive patients with locally advanced (IIIB) or metastatic (IV) NSCLC as 2nd or 3rd line therapy after failure of checkpoint-inhibitor regimens.
Step 2 (conditional phase III) comparative randomized phase III
Primary objective
To demonstrate that OSE2101 is superior to control treatment with respect to overall survival (OS) in HLA-A2 positive patients with locally advanced (IIIB) or metastatic (IV) NSCLC as 2nd or 3rd line therapy after failure of checkpoint-inhibitor regimens. |
|
| E.2.2 | Secondary objectives of the trial |
Step 1 (phase II) :
Secondary objectives
• To describe secondary measures of clinical efficacy including disease control rate (DCR) at 6 and 12 months, Health-related Quality of life and PFS, objective response rate (ORR) and evaluate duration of response (DR)
• To assess the safety and tolerability in the 2 treatment arms
• To describe patient reported outcomes (PRO) disease/treatment related symptoms of lung cancer, and general health status.
Step 2 (conditional phase III):
Secondary objectives
• To compare secondary measures of clinical efficacy including DCR at 6 months, Quality of life and PFS,
• To assess the safety and tolerability of OSE2101 compared to the control group
Exploratory objectives
• To compare other progression criteria ORR, DCR at 12 months, DR and PRO disease/treatment-related symptoms of lung cancer, and general health status in both treatment arms |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Protection of study subjects and compliance
1. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
2. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Demography
3. Female or male, 18 years of age or older.
Cancer Diagnosis and treatment
4. Histologically or cytologically proven diagnosis of NSCLC that is locally advanced (stage IIIB unsuitable for radiotherapy or metastatic (stage IV) according to the 7th edition of tumor, node, metastasis (TNM) in Lung Cancer published by the International Union Against Cancer and the American Joint Committee on Cancer.
5. Subjects with disease recurrence or progression
• After therapy with an immune checkpoint inhibitor and platinum based chemotherapy:
- either 1st line chemotherapy followed by 2nd line checkpoint inhibitor,
- or 1st line combination of checkpoint inhibitor and chemotherapy
6. Subjects with measurable or non-measurable lesions.
7. Subjects must express HLA-A2 phenotype as assessed serologically.
8. Subjects must be considered suitable for chemotherapy with either single-agent pemetrexed or docetaxel.
9. Subjects with brain metastases are eligible if treated (whole brain radiotherapy, stereotaxic radiotherapy, surgery) and have no symptoms have returned to baseline (except for signs and symptoms related to central nervous system therapy) for at least 2 weeks before initiation of allocated treatment and are not taking any forbidden medications (refer
to section 4.3.5 of the protocol).
10. Any prior chemotherapy, immunotherapy, radiation therapy or surgeries must have been completed at least 3 weeks prior to initiation of study medication.
11. Any toxicity from prior therapy must have recovered to ≤ Grade 1 (except alopecia).
Clinical status
12. ECOG performance status 0-1.
13. Adequate organ function as defined by all the following criteria:
a. Albuminemia > 25g/L
b. Serum aspartate transaminase (AST) and serum alanine transaminase
(ALT) ≤ 1.5 x upper limit of normal (ULN) with alkaline phosphatase ≤ 2.5 x ULN, or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to liver metastases
c. Total serum bilirubin ≤ 1.5 x ULN
d. Absolute neutrophil count (ANC) ≥ 1500/microliters
e. Platelets 100000/microliters
f. Hemoglobin ≥ 9.0 g/dL (in the absence of transfusion within 2 weeks before randomization)
g. Creatinine clearance (based on modified Cockcroft-Gault formula) ≥ 45 ml/min. |
|
| E.4 | Principal exclusion criteria |
Cancer Diagnosis and treatment
1. Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas). Large-cell carcinoma.
2. NSCLC that is predominantly squamous cell carcinoma, and patient had docetaxel as part of his prior chemotherapy.
3. Current or previous treatment with investigational therapy in another therapeutic clinical trial interrupted less than 4 weeks before study treatment initiation.
4. Patients whose tumor harbors EGFR gene mutation that sensitizes tumors to TKI (EGFR exon 18-21) or ALK rearrangement.
5. Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study).
6. Spinal cord compression (unless treated with the patient attaining good pain control and stable or recovered neurologic function), carcinomatous meningitis, or leptomeningeal disease
7. Patients with squamous cell histology or non-squamous cell histology previously treated by pemetrexed and with a contraindication for docetaxel with grade ≥ 2 neuropathy or hypersensitivity reaction to medications formulated with polysorbate 80 (Tween 80) as they could be randomly assigned to Arm B.
Medical history and clinical status
8. Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications.
9. Treatment with corticosteroids in the last 3-week period before inclusion, except for topical, ocular, intra-articular, intranasal, and
inhaled corticosteroids with minimal systemic absorption (e.g. with a dose ≤ 500 microgram beclomethasone equivalent for inhaled steroids), or adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent which are permitted.
10. A recognized immunodeficiency disease including human immunodeficiency virus (HIV) infection (and other cellular
immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary, congenital or
acquired immunodeficiencies).
11. Patients with auto-immune disease, with the exception of type I diabetes or treated hypothyroidism.
12. Patients with interstitial lung disease.
13. Patients with active B or C hepatitis.
14. Other malignancy: patients will not be eligible if they have evidence of active malignancy (other than non-melanoma skin cancer or localized cervical cancer, or localized and presumed cured prostate cancer).
15. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/orsponsor, excess risk associated with study
participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study.
16. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment (See APPENDIX 7
GUIDANCE ON CONTRACEPTION in the protocol)
17. Male patients sexually active with a woman of childbearing potential
must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator (See APPENDIX 7 GUIDANCE ON CONTRACEPTION in the protocol)
18. Breastfeeding women.
19. Women with a positive pregnancy test. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival (OS), basis for the statistical calculation of the number of subjects. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The study design is built as a 2 step Fleming design. Analysis of the 1st step will decide whether the 2nd step is warranted and analysis of the combined population included in step 1 and 2 is planned when the target
number of events is reached. |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints:
• Disease control rate (DCR) at 6 months based on RECIST1.1.
• QLQ-C30 (EORTC QLQ questionnaire): "Global health status/QoL" score based on questions 29 and 30.
• QLQ-LC13 (lung cancer module from EORTC QLQ questionnaire): time to 1st ≥ 10-point deterioration in chest pain, dyspnea or cough.
• Progression free survival based on RECIST1.1.
Exploratory endpoints:
• Objective Response Rate (ORR)
• DCR at 12 months.
• Duration of Response (DR).
• Time to deterioration (TTD) in patient reported chest pain, dyspnea and cough.
• Time to next lung cancer therapy. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The study design is built as a 2 step Fleming design. Analysis of the 1st step will decide whether the 2nd step is warranted and analysis of the combined population included in step 1 and 2 is planned when the target number of events is reached. |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Step1: randomized non-comparative one stage Fleming phase II/Step2: randomized comparative phase III |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 62 |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 6 |
| 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 |
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