Clinical Trials /

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

NCT02654587

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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 Locally Advanced (IIIB) Unsuitable for Radiotherapy or Metastatic (IV) Non-Small-Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: OSE2101C301
  • SECONDARY ID: 2015-003183-36
  • NCT ID: NCT02654587

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OSE2101Tedopi, EP-2101, EP2101, IDM-2101OSE2101
DocetaxelTaxotereDocetaxel or Pemetrexed
PemetrexedAlimtaDocetaxel or Pemetrexed

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
OSE2101ExperimentalOSE2101 will be administered as a 1 mL-subcutaneous injection on Day 1 every three weeks for six cycles, then every two months for the remainder of year one and finally every three months until unequivocal Recist 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal. OSE2101 dose will be 5 mg of peptide (0.5 mg for each peptide).
  • OSE2101
Docetaxel or PemetrexedActive ComparatorPatients 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
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          1. Signed and dated informed consent document indicating that the patient 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.

          3. Female or male, 18 years of age or older.

          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 i) either 1st line chemotherapy
             followed by 2nd line checkpoint inhibitor, or ii) 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 (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.

         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).

         12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

         13. 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:

          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
             Tyrosine-Kinase Inhibitor (TKI) (EGFR exon 18-21) or Anaplastic Lymphoma Kinase (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.

          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/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.

         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.

         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.

         18. Breastfeeding women.

         19. Women with a positive pregnancy test.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival time (OS)
Time Frame:Approx. 24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:6 months
Safety Issue:
Description:
Measure:QLQ-C30 (EORTC QLQ questionnaire): "Global health status/QoL" score based on questions 29 and 30
Time Frame:Approx. 24 months
Safety Issue:
Description:
Measure:QLQ-LC13 (lung cancer module from EORTC QLQ questionnaire): time to 1st ≥ 10-point deterioration in chest pain, dyspnea or cough
Time Frame:Approx. 24 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Approx. 24 months
Safety Issue:
Description:
Measure:Safety and tolerability profile compared to the control group
Time Frame:Approx. 24 months
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:OSE Immunotherapeutics

Trial Keywords

  • Non-Small-Cell Lung Cancer
  • NSCLC
  • Immunotherapy
  • Cancer vaccine
  • Metastasis

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