Clinical Trials /

Pembrolizumab in Combination With Platinum-based Doublet Chemotherapy in Patients With EGFR Mutation and ALK Positive NSCLC (Non-Small Cell Lung Cancer) With Progressive Disease Following Prior Tyrosine Kinase Inhibitors (TKIs)

NCT03242915

Description:

Investigators hypothesize that addition of pembrolizumab will enhance the efficacy of carboplatin and pemetrexed in EGFR (epidermal growth factor receptor) mutation and ALK (anaplastic lymphoma kinase) positive NSCLC patients who have disease progression following prior TKIs (tyrosine kinase inhibitors).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Combination With Platinum-based Doublet Chemotherapy in Patients With EGFR Mutation and ALK Positive NSCLC (Non-Small Cell Lung Cancer) With Progressive Disease Following Prior Tyrosine Kinase Inhibitors (TKIs)
  • Official Title: Phase II Multi-center Study of Pembrolizumab in Combination With Platinum-based Doublet Chemotherapy in Patients With EGFR Mutation and ALK Positive NSCLC (Non-Small Cell Lung Cancer) With Progressive Disease Following Prior Tyrosine Kinase Inhibitors (TKIs)

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.057
  • SECONDARY ID: HUM00129169
  • NCT ID: NCT03242915

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab/Carboplatin/Pemetrexed
CarboplatinPembrolizumab/Carboplatin/Pemetrexed
PemetrexedPembrolizumab/Carboplatin/Pemetrexed

Purpose

Investigators hypothesize that addition of pembrolizumab will enhance the efficacy of carboplatin and pemetrexed in EGFR (epidermal growth factor receptor) mutation and ALK (anaplastic lymphoma kinase) positive NSCLC patients who have disease progression following prior TKIs (tyrosine kinase inhibitors).

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab/Carboplatin/PemetrexedExperimentalPembrolizumab 200 mg with carboplatin at AUC (area under the curve dosing) 5 and pemetrexed at 500 mg/m2 administered intravenously every 3 weeks
  • Pembrolizumab
  • Carboplatin
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  Exon 19 deletion or Exon 21 L858R and L861Q or exon 18 G719X or S7681 EGFR mutation
             positive NSCLC patients with progressive and measurable disease.

          -  Tumor tissue for PD-L1 assessment should be available unless PD-L1 assessment results
             are already available.

          -  Patients should not have received any systemic chemotherapy for advanced NSCLC.
             Patients who have received neoadjuvant, adjuvant or as part of concurrent chemotherapy
             and radiation are eligible if they received the chemotherapy 12 months or more before
             the start of study therapy.

          -  ECOG PS 0-1 (Eastern Cooperative Oncology Group Performance Status: an attempt to
             quantify cancer patients' general well-being and activities of daily life. The score
             ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)

          -  Patients should have recovered to ≤ grade 1 from clinically meaningful (example
             alopecia is not considered clinically meaningful) adverse events related to prior
             treatments.

          -  Patients should be willing and able to provide written informed consent for the trial.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Demonstrate adequate organ function

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 1 week of enrollment.

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception

          -  Male subjects of child bearing potential must agree to use an adequate method of
             contraception

        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. If the half-life of the drug is
             known then starting therapy 5 half-lives after the end of the last therapy is
             acceptable.

          -  Has a diagnosis of immunodeficiency. Patient should not be of any immunosuppressive
             therapy or steroids > prednisone 10mg/day or its equivalent on the day of the start of
             therapy.

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Hypersensitivity to pembrolizumab, carboplatin or pemetrexed 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 targeted small molecule therapy, or palliative radiation therapy within 1 week
             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.

          -  Has a known additional malignancy that is progressing or requires active treatment or
             the treating physician believes will require therapy within 1 year.

          -  Has symptomatic central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years

          -  Has known history of non-infectious pneumonitis that required steroids or has current
             pneumonitis. Has known history of interstitial lung disease.

          -  Has an active infection requiring systemic therapy.

          -  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.

          -  Has 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 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.

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

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

          -  Has known active Hepatitis B or Hepatitis C

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

Primary Outcome Measures

Measure:The number of patients that respond to treatment
Time Frame:12 months
Safety Issue:
Description:The primary endpoint is Response Rate (RR) defined as the rate of complete and partial response. Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be non-pathological in size (<10mm short axis). Partial Response (PR): Persistence of one or more non-target lesion(s) but does not qualify for PD. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).

Secondary Outcome Measures

Measure:Progression free survival (PFS) time
Time Frame:12 months
Safety Issue:
Description:PFS is defined as the duration of time from registration to time of progression. Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).
Measure:Overall survival (OS) time
Time Frame:12 months
Safety Issue:
Description:Overall survival is defined as the time from registration to time of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Cancer Center

Last Updated

October 17, 2017