Study of OSE2101 Versus Standard Treatment as 2nd or 3rd Line in HLA-A2 Positive Patients With Advanced NSCLC After Failure of Immune Checkpoint Inhibitor

Study Overview
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Brief Summary
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The aim of this study is to determine if the Investigational Medicinal Product Tedopi (OSE2101) is more effective than standard treatment in treating patients with stage IIIB NSCLC unsuitable for radiotherapy or metastatic NSCLC in second- or third-line treatment after failure of immune checkpoint-inhibitor regimens.

Official Title
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A Randomized Parallel Group Phase III Trial of OSE2101 as 2nd or 3rd Line Compared With Standard Treatment (Docetaxel or Pemetrexed) in HLA-A2 Positive Patients With Advanced Non-Small-Cell Lung Cancer With Progressive Disease After Last Treatment With Immune Checkpoint Inhibitors (ICI). (OSE2101C301)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: OSE2101
* Drug: Docetaxel
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Female or male, 18 years of age or older. Histologically or cytologically proven diagnosis of NSCLC that is locally advanced (stage III) unsuitable for radiotherapy or metastatic (stage IV) according to the 8th edition of tumor, node, metastasis (TNM) in Lung Cancer published by the International Union Against Cancer and the American Joint Committee on Cancer. Subjects with disease recurrence or progression After therapy with an immune checkpoint inhibitor and platinum-based chemotherapy i) either 1st line chemotherapy followed by 2nd line checkpoint inhibitor, or ii) 1st line combination of checkpoint inhibitor and chemotherapy Patients with progression during or within 12 months after the end of ICI as sequential or concomitant platinum-based chemotherapy ± radiation for locally advanced disease (stage III) are eligible Subjects with measurable or non-measurable lesions. Subjects must express HLA-A2 phenotype as assessed serologically. Subjects must be considered suitable for chemotherapy with either single-agent pemetrexed or docetaxel. Subjects with brain metastases are eligible if treated (whole brain radiotherapy, stereotaxic radiotherapy, surgery) at least 3 weeks prior to initiation of study treatment and have no symptoms related to brain metastases for at least 2 weeks before initiation of study treatment and are not taking any forbidden medications. Any prior chemotherapy, immunotherapy, hormonal therapy, radiation therapy or surgeries must have been completed at least 3 weeks prior to initiation of study treatment. Any toxicity from prior therapy must have recovered to ≤ Grade 1 (except alopecia). Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Adequate organ function as defined by all the following criteria: Albuminemia > 25g/L 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 Total serum bilirubin ≤ 1.5 x ULN Absolute neutrophil count (ANC) ≥ 1500/L Platelets ≥ 100000/L Hemoglobin ≥ 9.0 g/dL (in the absence of transfusion within 2 weeks before randomization) Creatinine clearance (based on modified Cockcroft-Gault formula) ≥ 45 ml/min. Exclusion Criteria: Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas). Patients with squamous cell carcinoma histology, and who had docetaxel as part of his prior chemotherapy. Current or previous treatment with investigational therapy in another therapeutic clinical trial (interrupted less than 4 weeks before study treatment initiation). Patients whose tumor harbors EGFR gene mutation that sensitizes tumors to Tyrosine-Kinase Inhibitor (TKI) (EGFR exon 18-21) or Anaplastic Lymphoma Kinase (ALK) rearrangement. Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study). Spinal cord compression (unless treated with the patient attaining good pain control and stable or recovered neurologic function), carcinomatous meningitis, or leptomeningeal disease Patients with squamous cell histology or non-squamous cell histology previously treated by pemetrexed 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. Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications. 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 steroid doses ≤ 10 mg daily prednisone equivalent which are permitted. 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). Patients with auto-immune disease, with the exception of type I diabetes or treated hypothyroidism. Patients with interstitial lung disease. Patients with active B or C hepatitis. Other malignancy: patients will not be eligible if they have evidence of other active invasive cancer(s) (other than NSCLC) within 5 years prior to screening (except appropriately treated non-melanoma skin cancer or localized cervical cancer, or other local tumors considered cured (e.g.localized and presumed cured prostate cancer). Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study. 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. 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. Breastfeeding women. Women with a positive pregnancy test.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Step 1 primary objective: Overall Survival rate (approx. 100 patients) / Step 2 primary objective: Overall Survival (approx. 363 patients in total, number to be reassessed based on the step 1 results)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OSE2101<br>OSE2101 will be administered as a 1 mL-subcutaneous injection on Day 1 every three weeks for six cycles, then every eight weeks for the remainder of year one and finally every twelve weeks beyond year one until unequivocal RECIST 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal. Should pseudo progression or delayed response to treatment suspected in arm A, investigator may continue treatment beyond the time of RECIST-defined progression, if the patient is perceived to be experiencing clinical benefit. OSE2101 dose will be 5 mg of peptide (0.5 mg for each peptide). | Drug: OSE2101<br> <br> * Other names: IDM-2101;|
| Active Comparator: Docetaxel or Pemetrexed<br>Patients receiving docetaxel: Docetaxel 75 mg/m2 will be administered by intravenous infusion over 1 hour on Day 1 of a 21-day cycle. Patients receiving pemetrexed: Pemetrexed, 500 mg/m2, will be administered by intravenous infusion over 10 minutes on Day 1 of a 21-day cycle. Docetaxel and pemetrexed will be continued until unequivocal RECIST 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal. | Drug: Docetaxel<br> <br> * Other names: Taxotere;Drug: Pemetrexed<br> <br> * Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival time (OS) | In Step 1: OS rate at 12 months in experimental Arm A (OSE2101) in 84 evaluable patients exposed to OSE2101 In Step 2: comparison of OS between experimental Arm A (OSE2101) and control Arm B (docetaxel or pemetrexed) when 278 events observed | Approx. 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) at 6 months |  | 6 months | 
| QLQ-C30 (EORTC QLQ questionnaire): Global health status/QoL score based on questions 29 |  | Approx. 24 months | 
| QLQ-LC13 (lung cancer module from EORTC QLQ questionnaire): time to 1st ≥ 10-point deterioration in (question 40), dyspnea (questions 33, 34, 35) or cough (question 31) |  | Approx. 24 months | 
| Progression Free Survival (PFS) |  | Approx. 24 months | 
| Objective Response Rate (ORR) (in Step 1 only) |  | Approx. 24 months | 
| DCR at 12 months (in Step 1 only) |  | Approx. 24 months | 
| Duration of Response (DR) (in Step 1 only) |  | Approx. 24 months | 
| Safety and tolerability profile compared to the control group |  | Approx. 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Non-Small-Cell Lung Cancer, Immunotherapy, Cancer vaccine, Metastasis