Universal Cancer Peptide-based Vaccination in Metastatic NSCLC

Study Overview
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Brief Summary
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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
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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.

Official Title
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Anticancer Therapeutic Vaccination Using Telomerase-derives Universal Cancer Peptides in Metastatic Non Small Cell Lung Cancer : A Phase I/II Study

Conditions
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Metastatic Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: UCPVax


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UCPVax<br>UCPVax is a therapeutic cancer vaccine composed of two peptides called UCP2 and UCP4 derived from telomerase combined with Montanide ISA 51 VG as adjuvant. The two peptides UCP2 and UCP4 will be emulsified in Montanide ISA 51 and injected subcutaneously in separate sites (one site per peptide), at days 1, 8, 15, 29, 36 and 43 (priming phase) following by boost vaccination every 8 weeks for 12 months. | Drug: UCPVax<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) of UCPVax (phase I) | 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) | until day 57 after the first vaccination | 
| Dose-related immunogenicity (phase II) | Antigen-specific T cell responses measured using IFN-gamma ELISPOT. | at day 73 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | Tumor response evaluated per RECIST v1.1. | every 8 weeks up to 15 months | 
| Progression-free survival (PFS) | delay from the date of inclusion to the disease progression (RECIST) or death from any cause whichever occurs first, | through study completion, an average of 2 years | 
| Overall survival (OS) | delay from the date of inclusion to death from any cause. | through study completion, an average of 2 years | 
| Health related Quality of Life (QoL) | HrQoL will be assessed using EORTC QLQ-C30 and LC13 modules specific to lung cancer | through study completion, an average of 2 years | 
| Adverse Events according to NCI CTCAE v.4.03 |  | through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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telomerase, cancer immunotherapy, CD4 T lymphocyte helper