Non-small Cell Lung Cancer (NSCLC) Stage III
Conditions
Keywords
Non-small cell lung cancer (NSCLC), exploratory study, L-BLP25
Brief summary
Phase Ib study investigating whether liposome BLP25 mucin-1 (MUC1) peptide-specific immunotherapy (L-BLP25) administered as weekly subcutaneous doses over 8 weeks following a single dose of intravenous cyclophosphamide (CPA) induces a reproducible cytokine pattern measured in the serum of unresected Stage III non-small cell lung cancer (NSCLC) subjects after first-line chemo-radiation therapy.
Interventions
OTHERBiological: MUC1 peptide specific immunotherapy
Eight consecutive weekly subcutaneous administration with reconstituted L-BLP25 (containing 806 microgram of BLP25 lipopeptide) followed by administrations at 6-week intervals, commencing at Week 14, until disease progression is documented.
A single intravenous infusion of 300 milligram per square meter (to a maximum of 600 milligram) of CPA will be given three days before the first L-BLP25 administration.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented unresectable Stage III NSCLC, as defined by American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 7th edition (2009) criteria. All histological subtypes are acceptable, including bronchioalveolar carcinomas * Documented stable disease or objective response, according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.0, after primary chemo-radiotherapy (either sequential or concomitant) for unresected Stage III disease, within 4 weeks (28 days) prior to enrollment * Receipt of concomitant or sequential chemo-radiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of greater than equal to 50 Gray. Subjects must have completed the primary thoracic chemo-radiotherapy at least 4 weeks (28 days) and no later than 84 days prior to enrollment. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible * Platelet count greater than or equal to 140 \* 10\^9 per liter, white blood cell (WBC) greater than or equal to 2.5 \* 10\^9 per liter, and hemoglobin greater than or equal to 90 gram per liter * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 Additional Inclusion Criteria apply
Exclusion criteria
* Pre-therapies: * Previous lung cancer specific therapy (including surgery) other than primary chemo-radiotherapy * Receipt of immunotherapy within 4 weeks (28 days) prior to enrollment. Note: Subjects who have received monoclonal antibodies for imaging are acceptable * Receipt of investigational systemic drugs (including off-label use of approved products) within 4 weeks (28 days) prior to enrollment * Disease status: * Metastatic disease * Malignant pleural effusion at initial diagnosis and/or at trial entry * Past or current history of neoplasm other than lung carcinoma, except for curatively treated nonmelanoma skin cancer, in situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years * Autoimmune disease * A recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies * Any preexisting medical condition requiring systemic chronic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed) * Known Hepatitis B and/or C * Active infection at enrollment, including but not limited to, flu-like infections, urinary tract infections, bronchopulmonary infections, etc * Physiological functions: * Clinically significant hepatic dysfunction (that is, alanine aminotransferase \[ALT\] greater than 2.5 times normal upper limit \[ULN\]; or aspartate aminotransferase \[AST\] greater than 2.5 times ULN; or bilirubin greater than or equal to 1.5 \* ULN) * Clinically significant renal dysfunction (that is, serum creatinine greater than or equal to 1.5 \* ULN) * Clinically significant cardiac disease, for example, New York Heart Association (NYHA) Classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by an electrocardiogram (ECG) * Splenectomy * Infectious process that in the opinion of the investigator could compromise the subject's ability to mount an immune response Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immune response defined as change from baseline in serum cytokine levels after L-BLP25 administration at Week 1, 4 and 8 | Pre-dose (Day -3) up to 24 hours after L-BLP25 administration at Week 1, 4 and 8 |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of a cellular immune response following treatment with L-BLP25 | Pre-dose (Day -3) and at 24 hours after L-BLP25 administration at Week 4 and 8 |
| Change from baseline in alternative immune or inflammatory serum soluble immune mediators such as interferon alpha (IFNα), transforming growth factor beta (TGFβ), or C-reactive protein (CRP) at 6, 12, and 24 hours after L-BLP25 administration. | Pre-dose (Day -3) up to 24 hours after L-BLP25 administration at Week 1, 4 and 8 |
| Number of subjects with adverse events (AEs) | Up to 6 weeks after the last dose of L-BLP25 |
Outcome results
None listed