Phase II Study to Test Pembrolizumab (MK-3475) in First Line Treatment of Advanced NSCLC Patients With PD-L1 Low Tumors (<50%)_ PEOPLE TRIAL (Pembrolizumab in Pd-L1 Low Expressors).
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Non Small Cell Lung Cancer (NSCLC)
- Sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Immune biomarkers
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a prospective, monocentric, open label, phase II trial of intravenous (IV) Pembrolizumab monotherapy in subjects previously untreated for their stage IIIB-IV, PD-L1 low non small cell lung cancer (NSCLC).
Detailed Description
Approximately 65 subjects with PD-L1 low (PD-L1Lo), EGFR wt, EML4/ALK fusion negative NSCLC will be enrolled in this trial for examination of the biological characteristics associated to efficacy and safety of Pembrolizumab. Subjects will receive Pembrolizumab iv at dose of 200 mg every three weeks. Subjects will be evaluated every 9 weeks (63 +/- 3 days) with radiographic imaging to assess response to treatment. Subjects will continue with the assigned study treatment until RECIST-defined progression of disease, unacceptable toxicity or consent withdrawal. Treatment with Pembrolizumab will continue until two years of therapy have been administered, documented disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, or administrative reasons. Pembrolizumab treated subjects who obtain a confirmed Complete Response (CR) per RECIST 1.1 may consider stopping trial treatment. These subjects may be eligible for re-treatment with Pembrolizumab after they have experienced radiographic disease progression at the discretion of the investigator, this re-treatment will be the Second Course Phase.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a confirmed diagnosis of NSCLC in stage IIIB/ IV. Do not have an EGFR sensitizing (activating) mutation or ALK translocation and have a PD-L1 "low" (\<50%) tumor as determined by immunohistochemistry with anti-PD-L1 antibody (DAKO 22C3). Have not received prior systemic chemotherapy treatment for advanced NSCLC. Subjects with non-squamous histologies will not be enrolled until the EGFR mutation status and/or ALK translocation status is available. For patients enrolled who are known to have a tumor of predominantly squamous histology, molecular testing for EGFR and ALK translocation will not be required .
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be \>=18 years of age on day of signing informed consent.
- •Have measurable disease based on RECIST 1.
- •Be willing to provide tissue from archived histological specimen or newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 45 days prior to initiation of treatment on Day
- •Have a performance status of 0 or 1 on the ECOG Performance Scale.
- •Demonstrate adequate organ function
- •All screening labs should be performed within 10 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
Exclusion Criteria
- •The subject must be excluded from participating in the trial if the subject:
- •Has an EGFR sensitizing mutation and/or an ALK translocation.
- •Has a PD-L1 expression assessed as "high" by the central laboratory
- •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 antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •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.
- •Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Arms & Interventions
Pembrolizumab
subjects with PD-L1 low (PD-L1Lo), EGFR wt, EML4/ALK fusion negative NSCLC
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Immune biomarkers
Time Frame: 3 years
frequency of FOXP3+ lymphocytes, as well as of CD11b+ CD33+ MDSCs, in pre-therapy lesions
Secondary Outcomes
- Immune biomarkers distribution between pre and post Pembrolizumab treatment(3 years)
- Activity endpoints(3 years)
- Effectiveness of Pembrolizumab treatment(from the time of enrollment to death due to any reasons, assessed up to 3 years)
- Safety of Pembrolizumab treatment.(3 years)
- Patient Reported health status for physical, mental and social well-being(3 years)