Re-challenge Pembrolizumab Study as a Second or Further Line in Patients With Advanced NSCLC

Inclusion Criteria

• Patients with histologically or cythological confirmed NSCLC advanced or locally advanced disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) not amenable to radical treatment (IIIA, IIIB, IIIC, IV), squamous or non-squamous, recurrent after at least one prior line.
• The subject must be willing and able to provide written informed consent/assent for the trial.
• Patient must be aged ≥ 18 years of age on day of signing informed consent.
• Measurable disease (at least 1 lesion) based on RECIST 1.1. Patients will not be eligible if this lesion was irradiated before inclusion.
• Documented prior benefit (Stable Disease, Partial Response, Complete Response) to check point PD1/PDL1 inhibitor (Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab, Avelumab or others) for at least 16 weeks (Stable Disease, Partial Response, Complete Response) and progression while on treatment (or 12 weeks after stopping treatment (Cohort 2). No subsequent treatment before rechallenge is allowed in this cohort
• Patient must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. PDL1 must be evaluable and at least 1% positive in tumor tissue. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. Note: If a new sample core or excisional biopsy cannot be obtained but the patient can be included in the study and start the treatment and the archival tumor tissue could be sent afterwards for the central laboratory confirmation. If no previous PDL1 result is available from the archival tissue, the patient cannot be included in the trial until central laboratory PDL1 result is available. Other cases could be consulted with the trail chair.
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Demonstrate adequate organ function, all screening labs should be performed within 7 days of treatment initiation.
• 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.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception (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.

• Male subjects of childbearing potential must agree to use an adequate method of contraception (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.

• All patients will be required to submit a tumor sample for PD-L1 IHC expression. If the sample is inadequate for analysis, another sample could be provided. If a new sample cannot be obtained due to technical or clinical reasons, archival tissue can be sent. Other cases could be consulted with the trial chair.

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal