Clinical Trials /

Pembrolizumab in First Line Treatment of Advanced NSCLC Patients With PD-L1 Low Tumors.

NCT03447678

Description:

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).

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in First Line Treatment of Advanced NSCLC Patients With PD-L1 Low Tumors.
  • Official Title: 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).

Clinical Trial IDs

  • ORG STUDY ID: INT 178-17
  • NCT ID: NCT03447678

Conditions

  • Non Small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalsubjects with PD-L1 low (PD-L1Lo), EGFR wt, EML4/ALK fusion negative NSCLC
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. 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 .

          2. Be willing and able to provide written informed consent/assent for the trial.

          3. Be >=18 years of age on day of signing informed consent.

          4. Have measurable disease based on RECIST 1.1.

          5. 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 1.

          6. Have a performance status of 0 or 1 on the ECOG Performance Scale.

          7. Demonstrate adequate organ function

          8. All screening labs should be performed within 10 days of treatment initiation

          9. 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. 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

         11. Male subjects should 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

         12. No history of active malignancy requiring treatment

        Exclusion Criteria:

        The subject must be excluded from participating in the trial if the subject:

          1. Has an EGFR sensitizing mutation and/or an ALK translocation.

          2. Has a PD-L1 expression assessed as "high" by the central laboratory

          3. 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.

          4. Has a known history of active TB (Bacillus Tuberculosis).

          5. Hypersensitivity to Pembrolizumab or any of its excipients.

          6. 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.

          7. 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.

          8. Has a known additional malignancy that is progressing or requires active 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.

          9. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         10. Has a history of non-infectious pneumonitis that required steroids or has current
             pneumonitis.

         11. Has an active infection requiring systemic therapy.

         12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         13. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         18. Has received a live vaccine within 30 days of planned start of study therapy. Note:
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune biomarkers
Time Frame:3 years
Safety Issue:
Description:tumor infiltrating lymphocytes in patients whose tumors have a low PD_L1 expression

Secondary Outcome Measures

Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:tumor infiltrating lymphocytes in patients whose tumors have a low PD_L1 expression
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:infiltrating T cells that upregulate PD-1
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:inhibitory receptors such as TIM-3, LAG-3 and TIGIT
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:type of cells being positive for PD-L1(neoplastic cells vs infiltrating immune cells)
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:presence and phenotype of tumor-infiltrating lymphocytes in the pre-therapy lesions of patients with low expression of PD-L1
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:levels of CD3+, CD4+, CD8+ lymphocytes
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:expression, in TIL, of markers of functional differentiation to cytolytic stage such as granzyme B and TIA-1, or maturation to memory stage (CD45RO)
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:expression of PD1+ by TIL
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:expression of PD-L1 on neoplastic cells vs immune cells
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:expression of inhibitory receptors as LAG-3, TIM-3 and TIGIT
Measure:Immune biomarkers distribution between pre and post Pembrolizumab treatment
Time Frame:3 years
Safety Issue:
Description:frequency of FOXP3+ lymphocytes, as well as of CD11b+ CD33+ MDSCs, in pre-therapy lesions
Measure:Activity endpoints
Time Frame:from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease are objectively documented, assessed up to 3 years
Safety Issue:
Description:Response Duration (DoR)
Measure:Activity endpoints
Time Frame:3 years
Safety Issue:
Description:Objective Response Rate (ORR)
Measure:Activity endpoints
Time Frame:3 years
Safety Issue:
Description:Disease Control Rate (DCR)
Measure:Effectiveness of Pembrolizumab treatment
Time Frame:from the time of enrollment to death due to any reasons, assessed up to 3 years
Safety Issue:
Description:Overall Survival (OS) will be used as effectiveness endpoint
Measure:Safety of Pembrolizumab treatment.
Time Frame:3 years
Safety Issue:
Description:Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4. A particular attention will be placed in the evaluation of potential Immune related adverse events (IrAE)
Measure:Patient Reported health status for physical, mental and social well-being
Time Frame:3 years
Safety Issue:
Description:The patient Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental and social well-being from the patient prospective.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Last Updated

June 4, 2018