Metastatic Non-small Cell Lung Cancer
Conditions
Keywords
cancer immunotherapy, CD4 T lymphocyte helper, telomerase
Brief summary
UCPVAx is a therapeutic vaccine based on the telomerase-derived UCP designed to induce strong TH1 CD4 T cell responses in cancer patients. Three doses of UCPVax (0,25 mg, 0,5 mg and 1 mg) will be tested in this phase I/II study by using Continuous Reassessment Method (CRML) dose escalation design model. The phase I is a dose escalation study designed to evaluate safety of use of UCPVax and to estimate its Maximum Tolerated Dose (MTD). The phase II is a dose deescalation designed to evaluate the immunogenicity of UCPVax according to the dose level.
Detailed description
UCPVax study is a prospective multicenter phase I/II study: 54 patients with metastatic NSCLC will be enrolled in 5 centers in France. A translational research program will be performed to better define the eligibility criteria and predictive biomarkers needed for randomized phase II and Phase III trials.
Interventions
DRUGUCPVax
Sponsors
Invectys
Centre Hospitalier Universitaire de Besancon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other) * Stage IIIB not amenable to radiotherapy or stage IV cancer according to the TNM classification (7th edition) or recurrent NSCLC after surgery not amenable to loco-regional therapy. * Pre-treated with at least 2 or 3 lines of treatment (including immunotherapy). Chemoradiation for stage IIIB disease is considered as one treatment line. * At least one measurable lesion by CT scan or MRI based on RECIST criteria version 1.1 * Performance status 0 or 1 on the ECOG scale * Life-expectancy \> 3 months * Adequate hematological, hepatic, and renal function
Exclusion criteria
* Prior history of other malignancy except for: basal cell carcinoma of the skin, cervical intra-epithelial neoplasia and other cancer curatively treated with no evidence of disease for at least 5 years * Symptomatic brain metastases. Patients with controlled brain metastases after radiation therapy or with asymptomatic brain metastases may be included. * History of active autoimmune diseases (lupus, rheumatoid arthritis, inflammatory bowel disease…) * Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (prednisone or prednisolone ≤ 10 mg/day is allowed) - - Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C virus (HCV); presence in the serum of the antigens HBs * Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment * Pregnancy or lactating patients. * Patients with any medical or psychiatric condition or disease, * Patients under guardianship, curatorship or under the protection of justice.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) of UCPVax (phase I) | until day 57 after the first vaccination | The following adverse events graded according to CTCAE v 4.03 will be classified as DLTs : * Hematologic: * Grade 4 neutropenia (ANC \<0.5 x 109/L) lasting \>5 days; * Febrile neutropenia (defined as neutropenia ≥Grade 3 \[ANC \<1000 cells/mm3\] and a body temperature ≥38.5°C); * Grade ≥3 thrombocytopenia (\<50.0 - 25.0 x 109/L) with bleeding; * Grade 4 thrombocytopenia (\<25.0 x 109/L) \>5 days; * Grade 4 anemia (hemoglobin \<6.5 g/dL or 4.0 nmol/L); * Non-hematologic: o Grade ≥3 toxicities, except for alopecia and those grade 3 events that respond to treatment (eg. grade 3 nausea, vomiting, diarrhea that responds to standard medical supportive care within 48 hours will not be considered a DLT). * Immune system disorder: * Grade ≥2 allergic reaction (except for local reaction at the injection site : grade ≥ 3) * Grade ≥2 autoimmune disease (colitis, thyroidis…) * Grade ≥2 cytokine release syndrome (nausea, headache, tachycardia, hypotension, rash and shortness of breath) |
| Dose-related immunogenicity (phase II) | at day 73 | Antigen-specific T cell responses measured using IFN-gamma ELISPOT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | through study completion, an average of 2 years | delay from the date of inclusion to death from any cause. |
| Tumor response | every 8 weeks up to 15 months | Tumor response evaluated per RECIST v1.1. |
| Adverse Events according to NCI CTCAE v.4.03 | through study completion, an average of 2 years | — |
| Health related Quality of Life (QoL) | through study completion, an average of 2 years | HrQoL will be assessed using EORTC QLQ-C30 and LC13 modules specific to lung cancer |
| Progression-free survival (PFS) | through study completion, an average of 2 years | delay from the date of inclusion to the disease progression (RECIST) or death from any cause whichever occurs first, |
Countries
France
Outcome results
None listed