OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: OSE2101; Docetaxel; Pemetrexed
Intervention MeSH terms: Docetaxel; Pemetrexed
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two-step open-label study with a planned interim OS futility in experimental arm per Fleming design (Step1) Central randomisation (2:1) with stratification by histology (non-squamous versus squamous), best response to first-line treatment [complete response (CR) or partial response (PR) versus stable disease (SD) or PD] and line of prior anti-PD(L)1 treatment (first-line when combined with platinum-based chemotherapy versus second-line when administered as sequential treatment after first-line platinum-based chemotherapy).
Masking: None (Open Label)
Enrollment: 219.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Non-Small-Cell Lung Cancer; Therapeutic Cancer Vaccine; Resistance to Immunotherapy; Quality of Life

Summary:

      The aim of this clinical trial was to determine if the therapeutic cancer vaccine OSE2101
      (TEDOPI) was more effective than standard chemotherapy (docetaxel or pemetrexed) in treating
      HLA-A2 positive patients with metastatic NSCLC who progressed after sequential or concurrent
      chemotherapy and immune checkpoint inhibitor given in first or second-line treatment.

      The main questions were to compare the survival, the tolerance to treatment and the quality
      of life of patients between the two arms of treatment (OSE2101 versus standard chemotherapy)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed and dated informed consent

          2. Willingness and ability to comply with the clinical study procedures.

          3. Female or male, 18 years of age or older

          4. Histologically or cytologically proven diagnosis of Non-Small Cell Lung Cancer (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

          5. Subjects with disease recurrence or progression after immune checkpoint inhibitor and
             platinum-based chemotherapy:

             i) either 1st line chemotherapy followed by 2nd line immune checkpoint inhibitor, or
             ii) 1st line combination of immune checkpoint inhibitor and chemotherapy Patients with
             progression during or within 12 months after the end of immune checkpoint inhibitor
             given as sequential or concomitant platinum-based chemotherapy ± radiation for locally
             advanced disease (stage III) were eligible

          6. Subjects with measurable or non-measurable lesions according to RECIST 1.1

          7. Subjects must express HLA-A2 phenotype (central test in blood)

          8. Subjects must be considered suitable for chemotherapy with single-agent pemetrexed or
             single-agent docetaxel

          9. Subjects with brain metastases were 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

         10. Any prior chemotherapy, immunotherapy, hormonal therapy, radiation therapy or
             surgeries must have been completed at least 3 weeks prior to initiation of study
             treatment.

         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)

          2. Patients with squamous cell carcinoma histology, and who 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 with a contraindication for docetaxel with grade ≥ 2 neuropathy
             or hypersensitivity reaction to medications formulated with polysorbate 80 (Tween 80)

          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 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 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)

         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.