non-small cell lung cancer (NSCLC), resectable MedDRA version: 20.1 Level: PT Classification code 10029520 Term: Non-small cell lung cancer stage IIIA System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10029518 Term: Non-small cell lung cancer stage II
Conditions
Interventions
Trade Name: Keytruda
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Other descri
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Cooperation and willingness to complete all aspects of the study 2. Signed and dated written informed consent must be given prior to study inclusion 3. Histological or cytological confirmed NSCLC. 4. Clinical stage II-IIIA according to the TNM classification, 7th edition. stage IIIa: T1/T2 N2 (IIIa1-3 Robinson classification) 5. Adequate disease staging by PET/CT performed and resectability established. 6. At least 1 measurable lesion according to RECIST 1.1 7. Age = 18 years 8. ECOG performance status 0 - 1 9. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in in the protocol, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in protocol, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 11. Adequate bone marrow function, liver and renal function: a. Absolute neutrophil count = 1.5 x 10^9/L b. Thrombocytes = 100 x 10^9/L c. Hemoglobin = 9 g/dL without transfusion or EPO dependency (within 7 days of assessment) d. INR 1.5 X institutional ULN 12. Adequate lung and cardiac function for intended lung resection according to German S3 guideline Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery 2. Participation in a clinical trial within the last 30 days prior to study treatment 3. History of allogeneic tissue/solid organ transplant 4. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 5. Evidence of interstitial lung disease. 6. cT4 tumor 7. Symptomatic acute cardiovascular or cerebrovascular disease 8. Known active HBV, HCV or HIV infection 9. Has any other active infection requiring systemic therapy. 10. Patients with active tuberculosis 11. Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-Programmed cell death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) 12. A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 13. Patient has had a prior monoclonal antibody within 4 weeks prior to study Day 1 14. Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. [Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, he/she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.] 15. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study. 16. Has received a live vaccine within 30 days prior to the first dose of trial treatment. [Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.] 17. Has known hypersensitivity to pembrolizumab or any of constituents of the product. 18. Other active malignancy requiring treatment Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 19. Lactating or pregnant women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - feasibility and safety of a neoadjuvant application of pembrolizumab - antitumor activity of pembrolizumab with regard to clinical and pathologic tumor response ; Secondary Objective: - impact of neoadjuvant pembrolizumab on patient survival - explore potential predictive biomarkers for pembrolizumab efficacy - immune cell imaging ; Primary end point(s): The trial design will be a phase II trial, with descriptive outcome assessments of: • frequency and severity of adverse events including peri- and post-operative complications (grade 2-4 AEs according to NCI-CTCAE V4.03) • number of patients treated in compliance with protocol • Tumor response evaluation Clinical response parameters: o response rates (? tumor size / lymph node size), according to RECIST 1.1 criteria o ? PET-activity (standardized uptake value [SUV]) Pathologic response parameters: o Pathologic regression grading according to Junker criteria ;Timepoint(s) of evaluation of this end point: after relevant data for the respective endpoint has been collected and cleaned or at the end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • disease free survival • overall survival • prognostic value of tumor shrinkage • prognostic value of inflammatory infiltrates in and around the resected tumor • serum- and tumor tissue cytokine concentrations • multi-OMICS tissue analysis approach for markers and mechanisms ;Timepoint(s) of evaluation of this end point: after relevant data for the respective endpoint has been collected and cleaned or at the end of study | — |
Countries
Germany
Contacts
Public ContactDr. Aysun Karatas
AIO-Studien-gGmbH
Outcome results
None listed