Clinical Trials /

Plasma-Adapted First-Line Pembro In NSCLC

NCT04166487

Description:

This research study is studying to see if a blood test, collected at different times during the treatment of metastatic non-small lung cancer, can be used to detect early response in patients being treated with pembrolizumab and use that information to determine whether patients should continue treatment with pembrolizumab or switch treatment to pembrolizumab in combination with chemotherapy. The names of the study drugs involved in this study are: - Pembrolizumab - Platinum doublet chemotherapy, which may include the following: - Carboplatin and pemetrexed - Carboplatin and paclitaxel The name of the blood test: - InVision (Inivata, Ltd.)

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Plasma-Adapted First-Line Pembro In NSCLC
  • Official Title: Pilot Study of Serial Plasma Genotyping to Guide the Adaptive Treatment of Advanced NSCLC Receiving First-line Pembrolizumab

Clinical Trial IDs

  • ORG STUDY ID: 19-523
  • NCT ID: NCT04166487

Conditions

  • NSCLC Stage IV
  • Metastatic Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytruda®Pembrolizumab Cycles 1-2
PEMETREXEDAlimta®Pembrolizumab + Doublet Chemotherapy, Cycles 3+
CARBOPLATINParaplatin ®Pembrolizumab + Doublet Chemotherapy, Cycles 3+
PACLITAXELTaxol®,, OnxalPembrolizumab + Doublet Chemotherapy, Cycles 3+

Purpose

This research study is studying to see if a blood test, collected at different times during the treatment of metastatic non-small lung cancer, can be used to detect early response in patients being treated with pembrolizumab and use that information to determine whether patients should continue treatment with pembrolizumab or switch treatment to pembrolizumab in combination with chemotherapy. The names of the study drugs involved in this study are: - Pembrolizumab - Platinum doublet chemotherapy, which may include the following: - Carboplatin and pemetrexed - Carboplatin and paclitaxel The name of the blood test: - InVision (Inivata, Ltd.)

Detailed Description

      This is an open label, single institution, prospective pilot study.

      The purpose of this research study is to determine if a blood test, collected at different
      times during treatment, can be used to detect early response in patients being treated with
      pembrolizumab for lung cancer and use that information to determine whether patients should
      continue treatment with pembrolizumab or switch treatment to pembrolizumab in combination
      with chemotherapy.

      -The research study procedures include screening for eligibility and study treatment
      including evaluations approximately every 3 weeks.

      The names of the study drugs involved in this study are:

        -  Pembrolizumab

        -  Platinum doublet chemotherapy, which may include the following:

             -  Carboplatin and pemetrexed

             -  Carboplatin and paclitaxel

      The name of the blood test:

        -  InVision- Inivata

             -  This blood test that will help study how participants respond to the study
                treatment. ---

             -  Blood will be collected for this test at a few time points, both before and after
                participants receive treatment on study.

        -  Participants will be on the research study for up to 12 months.

        -  It is expected that about 40 people will take part in this research study.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab Cycles 1-2ExperimentalFor the first two cycles, Pembrolizumab will be administered at a predetermined dose every 3 weeks. InVision plasma draw will take place at Cycle 1 Day 1 and Cycle 2 Day 1, with return of results to the treating oncologist prior to Cycle 3 Day 1. At Cycle 3, patients will be re-registered per the inclusion criteria into 3 arms; PEMBROLIZUMAB Alone PEMBROLIZUMAB + Doublet Chemotherapy
  • Pembrolizumab
Pembrolizumab Alone, Cycle 3+Experimental- Following imaging assessment at Cycle 3, participants will continue pembrolizumab alone if the following responses are observed: Response of Partial Response/Complete Response Response of Stable Disease with plasma response Response of Progressive Disease without worsening cancer symptoms AND plasma response
  • Pembrolizumab
Pembrolizumab + Doublet Chemotherapy, Cycles 3+ExperimentalFollowing imaging assessment at Cycle 3, participants will receive pembrolizumab in combination with platinum doublet chemotherapy if they have a response of stable disease without plasma response, OR no plasma response and response of progressive disease without worsening cancer systems. Platinum doublet should be histology-appropriate and will be given on-label, per treating oncologist. PEMBROLIZUMAB Chemotherapy multiple agents systemic PEMETREXED CARBOPLATIN PACLITAXEL
  • Pembrolizumab
  • PEMETREXED
  • CARBOPLATIN
  • PACLITAXEL

Eligibility Criteria

        Inclusion Criteria:

        - Participants must have histologically or cytologically confirmed stage IV NSCLC (AJCC 8th
        edition).

        - Participants must have evaluable disease on imaging per RECIST (measurable disease is not
        required).

          -  No prior treatment with a systemic anti-cancer therapy of any kind for the treatment
             of stage IV NSCLC. Prior definitive chemoradiation for locally advanced disease, or
             prior adjuvant or neoadjuvant therapy for early stage disease is permitted if
             completed ≥6 months prior to initiating study treatment.

          -  Age ≥18 years.

          -  ECOG performance status 0-2 (see Appendix A)

          -  Candidate for combination chemoimmunotherapy per physician assessment.

          -  Participants must have normal organ and marrow function as defined below:

             -- absolute neutrophil count ≥1000/mcL

               -  platelets ≥100,000/mcL

               -  total bilirubin <1.3 mg/dL

               -  creatinine <1.6 mg/dL

          -  PD-L1 tumor proportion score (TPS) ≥1%, as determined by a CLIA-laboratory.

          -  The effects of pembrolizumab on the developing human fetus are unknown. For this
             reason and because immune checkpoint blockade agents as well as other therapeutic
             agents used in this trial are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while she or
             her partner is participating in this study, she should inform her treating physician
             immediately. Men treated or enrolled on this protocol must also agree to use adequate
             contraception prior to the study, for the duration of study participation, and 4
             months after completion of pembrolizumab administration.

             -- NOTE: a pregnancy test will be required at screening for women of childbearing
             potential.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Inclusion Criteria for Treatment Continuation at Cycle 3 -- Completion of repeat
             plasma NGS (InVision) on study, with plasma response defined as ≥50% reduction in
             plasma ctDNA max AF between C1D1 and C2D1 for patients with high shed [≥0.5% max AF]
             at C1D1, or continued low shed [<0.5% max AF] for patients with low shed at C1D1.

               -  Completion of restaging scans on study, with response determined by central
                  review per RECIST 1.1 criteria

               -  For participants continuing pembrolizumab alone:

                    -  Response of Partial Response or Complete Response at Cycle 3 imaging
                       assessment (as determined by TIMC).

        OR --- Response of Stable Disease at Cycle 3 imaging assessment (as determined by TIMC) AND
        plasma response.

        OR

          -  Response of Progressive Disease at Cycle 3 imaging assessment (as determined by TIMC)
             without worsening cancer symptoms (as determined by the treating investigator) AND
             plasma response.

             -- For participants continuing pembrolizumab + doublet chemotherapy:

          -  Response of Stable Disease at Cycle 3 imaging assessment (as determined by TIMC) AND
             no plasma response.

        OR --- Response of Progressive Disease at Cycle 3 imaging assessment (as determined by
        TIMC) without worsening cancer symptoms (as determined by the treating investigator) AND no
        plasma response.

        - NOTE: Patients with a response of Progressive Disease at Cycle 3 imaging assessment (as
        determined by TIMC) with worsening cancer symptoms (as determined by the treating
        investigator) must come off treatment.

        Exclusion Criteria:

          -  Participants with known sensitizing alterations in EGFR, ALK, ROS1 or BRAF.

          -  Participants who have had chemotherapy or radiotherapy within 1 week prior to entering
             the study.

          -  Participants who are receiving any other investigational agents.

          -  Participants with uncontrolled brain metastases, leptomeningeal disease, or spinal
             cord compression. Patients with asymptomatic untreated brain metastases are eligible.
             Patients with treated CNS disease are eligible if stable disease is clinically
             confirmed ≥2 weeks after definitive CNS therapy (radiation or surgery), and the
             patient is not receiving systemic steroids ≥10mg of prednisone equivalent at the time
             of enrollment.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to pembrolizumab or other agents used in study.

          -  Ongoing or active autoimmune disease requiring systemic steroids of ≥10mg of
             prednisone equivalent or other systemic immunomodulatory agents at the time of
             enrollment. Type I diabetes mellitus, hypothyroidism only requiring hormone
             replacement, skin disorders (such as psoriasis, vitiligo, and alopecia) not requiring
             systemic therapy, or conditions not expected to recur in the absence of an external
             trigger are allowed.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because pembrolizumab is a Pregnancy
             Category D agent with the potential for teratogenic or abortifacient effects. Because
             there is an unknown but potential risk for adverse events in nursing infants secondary
             to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if
             the mother is treated with pembrolizumab. These potential risks may also apply to
             other agents used in this study.

          -  Participants with a known history of testing positive for human immunodeficiency virus
             (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded from this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:6-month Progression Free Survival rate
Time Frame:6 Months
Safety Issue:
Description:Kaplan-Meier method

Secondary Outcome Measures

Measure:Early Plasma Response
Time Frame:42 Days
Safety Issue:
Description:Early plasma response is defined as ≥50% reduction in plasma ctDNA max AF between C1D1 and C2D1 for patients with high shed [≥0.5% max AF] at C1D1, or persistent low shed [<0.5% max AF] for patients with low shed at C1D1
Measure:Progression Free Survival
Time Frame:he time from registration to the earlier of progression or death due to any cause or 30 Months
Safety Issue:
Description:Kaplan-Meier method will be used to estimate event-time distributions and medians for time-to-event data
Measure:Overall Survival
Time Frame:time from registration to death from any cause, and patients who are thought to be alive at the time of final analysis will be censored at the last date of contact or 30 months
Safety Issue:
Description:Kaplan-Meier method will be used to estimate event-time distributions and medians for time-to-event data
Measure:Feasibility-adherence to protocol therapy for 4 cycles
Time Frame:84 Days
Safety Issue:
Description:Feasibility is defined as a patient's adherence to protocol therapy for 4 cycles

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • NSCLC Stage IV
  • Metastatic Non-Small Cell Lung Cancer

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