It will be conducted in stage IIIB/IV NSCLC cancer patients with documented stable disease or objective response according to RECIST criteria after initial chemotherapy or chemo-radiotherapy
Conditions
Interventions
Product Name: Curevac
Product Code: CV9201
Pharmaceutical Form: Solution for injection
Current Sponsor code: CV9201-1, CV9201-2, CV9201-3, CV9201-4, CV9201-5
Other descriptive name: CTAG1B, MAGEC2, MA
Sponsors
CureVac GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female and age = 18 yrs and = 75 2. Histologically or cytologically confirmed and documented stage IIIB/IV NSCLC 3. Documented stable disease or objective response according to RECIST criteria after initial chemotherapy or chemo-radiotherapy for advanced, unresectable disease: • Patients must have received a minimum of two cycles of standard chemotherapy, and adequate and effective radiotherapy if used in conjunction with chemotherapy (sequentially or concomitantly). Prophylactic brain radiation is allowed. • Surgery, radiotherapy and/ or chemotherapy can have been previously administered for non-advanced disease. • All therapies must be completed 4 weeks before start of study treatment. 4. Performance status: Eastern Cooperative Oncology Group (ECOG) 0 – 1. 5. Life expectancy > 6 months as assessed by the investigator. 6. Adequate organ function: • Bone marrow function: hemoglobin = 100 g/L; white blood cell count (WBC) = 3.0 x 10 9/L; lymphocyte count = 1.0 x 10 9/L; absolute neutrophil count (ANC) = 1.5 x 10 9/L; platelet count = 100 x 10 9/L • Hepatic: aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 times upper limit of normal (ULN) (=5 x ULN if hepatic metastases present); bilirubin = 1.5 x ULN • Renal: creatinine = 2 mg/dL and creatinine clearance = 45 mL/min 7. Patients of child-producing potential must agree to use contraception while enrolled in the study and for one month after the last immunization 8. Written informed consent must be obtained prior to conducting any study-specific procedures Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. History of anti-cancer therapy for advanced disease other than initial chemotherapy or chemo-radiotherapy or surgery 2. Immunotherapy within 4 weeks prior to study enrollment, including cytokines such as granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF) or interferons 3. Treatment with investigational anti-cancer agents during initial therapy for advanced disease or any investigational agents within 4 weeks prior to study enrollment 4. Concurrent anti-tumor therapy or concurrent immunotherapy such as lectins, unspecific immunostimulants, etc. 5. Previous anti-cancer immunotherapy comprising RNA-transfected dendritic cells or DNA vaccines targeting any tumor-associated antigens. 6. Concurrent systemic steroids except topical (inhaled, topical, nasal) for the last 28 days, except replacement therapy 7. Concurrent major surgery or planned surgery 8. Prior splenectomy 9. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy such as sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis or systemic vasculitis (except autoimmune thyroiditis with only thyroid hormone replacement and stable disease > 1 year) 10. Primary or secondary immune deficiency 11. Active allergy requiring continuous medication or active infections requiring anti-infectious therapy 12. Seropositive for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 13. History of other malignancies over the last 5 years (except basal cell carcinoma of the skin or carcinoma in situ of the cervix) 14. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, known ascites and/or uncontrolled pleural effusion. 15. Brain metastases (symptomatic or asymptomatic) or leptomeningeal involvement 16. Symptomatic congestive heart failure (New York Heart Association [NYHA] 3 or 4); unstable angina pectoris within 6 months prior to enrollment; significant cardiac arrhythmia, history of stroke or transient ischemic attack 17. History of seizures, encephalitis or multiple sclerosis 18. Gastric ulcer or inflammatory bowel disease or Crohn´s disease or ulcerative colitis; no active diverticulitis 19. Active drug abuse or chronic alcoholism 20. Patients being committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I part: Primary: Determination of recommended dose (RD) for exploration in the phase IIa part of the study. Phase IIa part: Assessment of safety and tolerability of the trial regimen ;Secondary Objective: Phase I part: Assessment of safety of the treatment regimen Evaluation of induction of immune response Assessment of anti-tumor activity. Phase IIa part: Evaluation of induction of immune response. Asessment of anti-tumor actvity. Correlation between tumor-associated antigen (TAA) expression and survival/progression/immunological response.;Primary end point(s): Phase I: Primary endpoint:Occurrence of DLT between treatment initiation and the week 5 visit in patients evaluable for determination of RD. Additional endpoints in the phase I part of the study are the same as those listed below for the phase IIa part. Phase IIa: Safety endpoints (evaluated in the treated population): •incidence and severity of treatment-related adverse events and laboratory abnormalities, graded according to NCI-CTCAE version 3.0 criteria •occurrence of Serious Adverse Events •occurrence of treatment discontinuation due to treatment-related adverse events •incidence of treatment-emergent autoimmune disease or development of autoimmune antibodies Immune endpoints (evaluable for immune response population): •rate of vaccine antigen-specific cellular and humoral immune response (ELISpot and ELISA assessment of immune reaction to vaccine antigens) at weeks 5 and 9 phase I only, and at end of treatment compared to baseline •evolution of regulatory T cell levels during the course of treatment Efficacy endpoints: •objective disease response in patients evaluable for RECIST response •progression-free survival, from initiation of vaccine and from initiation of initial chemotherapy •overall survival, from initiation of vaccine and from initiation of initial chemotherapy •evaluation of carcinoembryonic antigen / cytokeratin fragment 21-1 (CEA/CYFRA 21-1) tumor | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Additional endpoints in the phase I part of the study are the same as those listed in E.5.1 for the phase IIa part.;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Germany, Switzerland
Contacts
Public ContactKarl-Josef Kallen
CureVac GmbH
Outcome results
None listed