Pembrolizumab Alone versUs pembrolizumab-chemotherapy in first LInE NSCLC

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 84

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
•Histologically confirmed NSCLC, negative for EGFR mutations and ALK fusions, no molecular testing is required in squamous NSCLCECOG Performance Scale 0-2
•Be willing and able to provide written informed consent for the trial
•Be 18 years or older of age on the day of signing informed consent
•Have measurable disease based on RECIST v1.1
•Must provide tissue from a histological tumor biopsy that was not yet irradiated
•High tumor PD-L-1 expression (=50% TPS)
•High tumor burden (=2 extrapulmonary metastases (M1c)) and not amenable for local consolidative therapies
•Must have adequate hematologic and organ function, defined by the following laboratory results:
•- Absolute neutrophil count (ANC) = 1500 cells/µL
•- WBC count = 2000 cells/µL
•- Platelet count = 100.000/µL
•- Hemoglobin = 5.6 mmol/L
•- AST and ALT = 3 x ULN (= 5 x ULN if liver metastases are present)
•- Serum bilirubin = 1.5 x ULN (except subjects with known Gilbert disease, who can have total bilirubin < 3.0 mg/dL)
•- Serum Creatinine = 1.5 x ULN OR measured of calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) = 40 mL/min for subject with creatinine levels > 1.5 x ULN.

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
•Patients amenable for local consolidative therapies
•Use of steroids equivalent to >10 mg prednisolon per day prior to start of study or other immunosuppressive medications within 14 days prior. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
•Untreated brain metastases
•Uncontrolled active infections, HIV, active Hepatitis B or C
•Autoimmune diseases and interstitial lung diseases are to be excluded depending on physicians decision
•A known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
•Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
•Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening.
•Prior systemic therapy for the NSCLC using chemotherapy or immunotherapy with prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
-to assess the effect of chemotherapy given concurrently with pembrolizumab on overall response rate (ORR) in NSCLC patients with high PD-L1 and high tumor burden

Secondary Outcome Measures

Name	Time	Method
-to examine the effect of chemotherapy given concurrently with pembrolizumab on progression free survival (PFS) and overall survival (OS) in patients with high PD-L1 and high tumor burden as compared to pembrolizumab monotherapy followed by chemotherapy at progression<br>-to compare the PFS of concurrent chemo-pembrolizumab with sequential pembrolizumab followed by chemotherapy at progression (i.e. PFS-1 plus PFS-2)