Clinical Trials /

Chemotherapy With Pembrolizumab Continuation After Progression to PD-1/L1 Inhibitors

NCT03656094

Description:

After progression to previous PD-1/L1 inhibitors (pembrolizumab, nivolumab, or atezolizumab), physicians' choice chemotherapy plus pembolizumab (or placebo) will be administered (3 weeks per cycle) until disease progression or unacceptable toxicity.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Chemotherapy With Pembrolizumab Continuation After Progression to PD-1/L1 Inhibitors
  • Official Title: Chemotherapy Plus Pembrolizumab After Progression With Previous PD-1/PD-L1 Inhibitors in Patients With Advanced Non-small Cell Lung Cancer: Placebo-controlled Randomized Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: SMC 2018-07-044
  • NCT ID: NCT03656094

Conditions

  • Non-small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
Pembrolizumab plus chemotherapyChemotherapy: one of docetaxel, pemetrexed, or vinorelbinePembrolizumab plus chemotherapy
Placebo plus chemotherapychemotherapy: one of docetaxel, pemetrexed, or vinorelbinePlacebo plus chemotherapy

Purpose

After progression to previous PD-1/L1 inhibitors (pembrolizumab, nivolumab, or atezolizumab), physicians' choice chemotherapy plus pembolizumab (or placebo) will be administered (3 weeks per cycle) until disease progression or unacceptable toxicity.

Detailed Description

      Previous PD-1/PD-L1 inhibitors should be 2nd or 3rd line therapy for advanced NSCLC. There
      should be no systemic therapy after previous PD-1/PD-L1 therapy, before the enrollment to
      this study.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab plus chemotherapyExperimentalPembrolizumab (200 mg) plus chemotherapy (physicians' choice among docetaxel, pemetrexed, or vinorelbine) every 3 weeks
  • Pembrolizumab plus chemotherapy
Placebo plus chemotherapyActive ComparatorPlacebo plus chemotherapy (physicians' choice among docetaxel, pemetrexed, or vinorelbine) every 3 weeks
  • Placebo plus chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          1. Male /female participants who are at least 20 years of age on the day of signing
             informed consent with histologically confirmed diagnosis of

          2. Histologically confirmed non-small cell carcinoma

          3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the date of
             allocation/randomization.

          4. Received one or two cytotoxic chemotherapy for advanced NSCLC including at least one
             platinum-doublet

          5. Has received prior therapy with an anti-PD-1, anti-PD-L1 agents (monotherapy) and
             progression to last PD-1/PD-L1 inhibitors. The last PD-1/PD-L1 inhibitor should be
             administered 6 weeks before the study enrollment, and no other systemic therapy should
             be done between the interval.

          6. At least one measurable lesion Have measurable disease based on RECIST 1.1. Lesions
             situated in a previously irradiated area are considered measurable if progression has
             been demonstrated in such lesions.

          7. Available data for PD-L1 IHC results (any of one tested by 22C3, SP263, or SP142)
             irrespective of expression level.

          8. EGFR and ALK wild type

        Exclusion Criteria:

          1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
             [randomization/allocation] (see Appendix 3). If the urine test is positive or cannot
             be confirmed as negative, a serum pregnancy test will be required.

          2. Has received prior systemic anti-cancer therapy including investigational agents
             within 3 weeks [could consider shorter interval for kinase inhibitors or other short
             half-life drugs] prior to [randomization /allocation].

             Note: Participants must have recovered from all AEs due to previous therapies to
             ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

             Note: If participant received major surgery, they must have recovered adequately from
             the toxicity and/or complications from the intervention prior to starting study
             treatment.

          3. Has received prior radiotherapy within 2 weeks of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

          4. Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

          5. Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 3 weeks prior to the first dose of
             study treatment.

             Note: Participants who have entered the follow-up phase of an investigational study
             may participate as long as it has been 4 weeks after the last dose of the previous
             investigational agent.

          6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          7. Has a known additional malignancy that is progressing or has required active treatment
             within the past 2 years. Note: Participants with basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, well differentiated thyroid carcinoma, or
             carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone
             potentially curative therapy are not excluded.

          8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
             previously treated brain metastases may participate provided they are radiologically
             stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
             (note that the repeat imaging should be performed during study screening), clinically
             stable and without requirement of steroid treatment for at least 14 days prior to
             first dose of study treatment. Patients with oligo (≤5) brain metastasis with size
             less than 1cm can be enrolled without prior radiotherapy, if the tumors are regarded
             as asymptomatic and stable, based on follow-up brain MRIs checked intervals of at
             least 3 months. However, all patients with previously non-irradiated brain metastases
             should have brain MRI checked within 4 weeks before starting administration of study
             drugs.

          9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any PD-1/PD-L1
             inhibitors.

         10. 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.

         11. Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

         12. Has an active infection requiring systemic therapy.

         13. Has a known history of Human Immunodeficiency Virus (HIV)

         14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
             detected) infection.

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

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

         17. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:up to 60 moths
Safety Issue:
Description:Time interval from enrollment to disease progression or death

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:up to 60 months
Safety Issue:
Description:Partial reseponse is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions
Measure:Overall survival (OS)
Time Frame:60 months
Safety Issue:
Description:Time interval between enrollment to death of any cause
Measure:Toxicity by CTCAE
Time Frame:60 months
Safety Issue:
Description:AEs graded using CTCAE (Version 4.0) criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Samsung Medical Center

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