Clinical Trials /

Adjuvant Pembrolizumab vs Observation Following Curative Resection for Stage I Non-small Cell Lung Cancer (NSCLC) With Primary Tumors Between 1-4 cm

NCT04317534

Description:

A randomized trial of adjuvant Pembrolizumab following surgical resection versus observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm. Patients will be randomized (1:1) 4-12 weeks following surgery to either: - Arm A: Pembrolizumab 400 mg every 6 weeks × 9 cycles - Arm B: Observation Stratification factors will include: PD-L1 TPS (<50% vs. ≥50%), and tumor size (1-2 cm vs. >2-4 cm)

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Pembrolizumab vs Observation Following Curative Resection for Stage I Non-small Cell Lung Cancer (NSCLC) With Primary Tumors Between 1-4 cm
  • Official Title: A Randomized Phase II Trial of Adjuvant Pembrolizumab Versus Observation Following Curative Resection for Stage I Non-small Cell Lung Cancer (NSCLC) With Primary Tumors Between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-LUN18-153
  • NCT ID: NCT04317534

Conditions

  • NSCLC, Stage I

Interventions

DrugSynonymsArms
PembrolizumabArm A- Pembrolizumab

Purpose

A randomized trial of adjuvant Pembrolizumab following surgical resection versus observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm. Patients will be randomized (1:1) 4-12 weeks following surgery to either: - Arm A: Pembrolizumab 200 mg every 3 weeks × 17 cycles - Arm B: Observation Stratification factors will include: PD-L1 TPS (<50% vs. ≥50%), and tumor size (1-2 cm vs. >2-4 cm)

Detailed Description

      A randomized trial of adjuvant Pembrolizumab following surgical resection versus observation
      following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with
      primary tumors between 1-4 cm.

      Patients will be randomized (1:1) 4-12 weeks following surgery to either:

        -  Arm A: Pembrolizumab 200 mg every 3 weeks × 17 cycles

        -  Arm B: Observation

      Stratification factors will include: PD-L1 TPS (<50% vs. ≥50%), and tumor size (1-2 cm vs.
      >2-4 cm)

      Primary Objective:

        -  To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection
           improves disease free survival compared with observation following surgical resection in
           patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4
           cm in size, regardless of PD-L1 TPS score.

      Secondary Objectives:

        -  To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection
           improves overall survival compared with observation in patients with stage I non-small
           cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size, regardless of PD-L1
           TPS.

        -  To evaluate the disease-free survival and overall survival rates at 1 year, 2 years, and
           3 years on each arm.

        -  To characterize the toxicity profile of adjuvant Pembrolizumab following surgical
           resection in patients with stage I non-small cell lung cancer (NSCLC) with primary
           tumors between 1-4 cm in size.

      Exploratory Objectives:

        -  To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection
           improves disease free survival compared with observation following surgical resection in
           patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4
           cm in size and a PD-L1 tumor proportion score (TPS) of ≥ 50%.

        -  To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection
           improves disease free survival compared with observation following surgical resection in
           patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4
           cm in size and a high tumor mutation burden (TMB) defined as ≥ 10 mutations/MB.

        -  To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection
           improves disease free survival compared with observation following surgical resection in
           patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4
           cm in size and a high tumor mutation burden (TMB) defined as ≥ 16 mutations/MB.

        -  To evaluate the disease free survival and overall survival for patients stratified by
           PD-L1 status (TPS ≥ 50% vs. < 50%), and tumor size (1-2 cm vs. >2-4 cm).

        -  To evaluate the association between various known prognostic variables, including, but
           not limited to, tumor differentiation (well-differentiated, moderately well
           differentiated, poorly differentiated), lymphovascular invasion, sex (male, female), PET
           max SUV and disease free survival and overall survival in patients treated with adjuvant
           Pembrolizumab for stage I non-small cell lung cancer (NSCLC) with primary tumors between
           1-4 cm in size.

        -  To evaluate whether the presence of circulating tumor DNA (ctDNA) or circulating tumor
           cells (CTCs) following surgical resection predicts relapse in patients with stage I
           non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size.

        -  To evaluate whether the presence of ctDNA or CTCs following surgical resection in
           patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4
           cm in size can predict which patients benefit from adjuvant Pembrolizumab compared to
           observation.

        -  To evaluate potential biomarkers (which may include genomics, RNA, tumor infiltrating
           lymphocytes, CD4 and CD8 expression, JAK2, STK11/LB1 loss of function, macrophage
           profile, neutrophil/lymphocyte ratio, and microbiome) as prognostic or predictive for
           improved disease free survival and overall survival.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A- PembrolizumabExperimentalPembrolizumab 200mg IV every 3 weeks x 17 cycles
  • Pembrolizumab
Arm B - ObservationNo InterventionObservation only

    Eligibility Criteria

            Inclusion Criteria:
    
              -  The participant (or legally acceptable representative if applicable) must provide
                 written informed consent for the study. The participant may also provide consent for
                 future unspecified research samples. However, the participant may participate in the
                 study without participating in the future unspecified research sample collection.
    
              -  Males and females age ≥ 18 years at the time of consent.
    
              -  ECOG Performance Status of 0-1 within 28 days prior to registration.
    
              -  Patients must have undergone complete surgical resection of their stage I NSCLC
                 between 4-12 weeks prior to registration and have negative surgical margins (R0).
    
                   -  NOTE: Both squamous and non-squamous histologies are allowed into the study.
                      Cancers with a histology of "adenosquamous" are considered a type of
                      adenocarcinoma and thus "non-squamous histology".
    
                   -  NOTE: Staging will be according to the AJCC 8th edition.
    
              -  Pathological tumor size must be 1.0 - 4.0 cm in greatest dimension.
    
              -  Surgery for this lung cancer must be completed at least 28 days prior to registration.
    
              -  Must have either previous NGS and PD-L1 results available using the Dako 22C3 antibody
                 or have archival tissue of surgical specimen from current diagnosis available to
                 perform analyses. If prior PD-L1 results with Dako 22C3 antibody are not available
                 from a CLIA-accredited laboratory, subjects must be able to provide 5µm x 4unstained
                 slides for prospective analysis to be used for stratification. If NGS results are not
                 available, subjects must be able to provide at least 10 x 10µm unstained and 1 x 4µm
                 H&E slides from current diagnosis for future NGS and/or other genetic analyses.
    
              -  Demonstrate adequate organ function as defined in the protocol; all screening labs to
                 be obtained within 28 days prior to registration.
    
              -  Females of childbearing potential must have a negative urine or serum pregnancy test
                 within 72 hours prior to registration. If the urine test is positive or cannot be
                 confirmed as negative, a serum pregnancy test will be required. For subjects
                 randomized to the pembrolizumab arm: If there is > 72 hours between the screening test
                 and C1D1, another pregnancy test (urine or serum) must be performed and must be
                 negative before the subject may start C1D1.
    
                   -  NOTE: Females are considered of childbearing potential unless: they are
                      postmenopausal; are surgically sterile; or they have a congenital or acquired
                      condition that prevents childbearing. See Section 5.1.4 for definitions.
    
                   -  NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred
                      contraception for the subject.
    
              -  A female participant is eligible to participate if she is not pregnant, not
                 breastfeeding, and at least one of the following conditions applies:
    
                   -  Not a woman of childbearing potential (WOCBP) OR
    
                   -  A WOCBP who is using a highly effective contraceptive method (failure rate of <1%
                      per year), or is abstinent from heterosexual intercourse as their preferred and
                      usual lifestyle (abstinent on a long term and persistent basis) during the
                      intervention period and for at least 120 days after the last dose of study drug.
                      The investigator should evaluate the potential for contraceptive method failure
                      (i.e., noncompliance, recently initiated) in relationship to the first dose of
                      study drug. See contraceptive guidance in Section 5.1.4 of the protocol.
    
              -  As determined by the enrolling physician or protocol designee, ability of the subject
                 to understand and comply with study procedures for the entire length of the study
    
            Exclusion Criteria:
    
              -  Current lung cancer is <1 cm or > 4 cm in size or is stage II, III, or IV.
    
              -  Patients with tumors that are known to harbor actionable EGFR mutations.
    
              -  Prior chemotherapy, radiation therapy, or immunotherapy for the treatment of this lung
                 cancer.
    
              -  Has a known additional malignancy that is progressing or has required active treatment
                 within the past 3 years. NOTE: Participants with basal cell carcinoma of the skin,
                 squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma in
                 situ, cervical cancer in situ) that have undergone potentially curative therapy are
                 not excluded.
    
              -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent
                 directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40,
                 CD137).
    
              -  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.
    
              -  Is currently participating in or has participated in a study of an investigational
                 agent or has used an investigational device within 4 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.
    
              -  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 randomization.
    
              -  Has had an allogenic tissue/solid organ transplant.
    
              -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
    
              -  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.
    
              -  Has a history of (non-infectious) pneumonitis that required steroids or has current
                 pneumonitis.
    
              -  Has an active infection requiring systemic therapy.
    
              -  Has a known history of Human Immunodeficiency Virus (HIV). Note: HIV testing is not
                 required unless mandated by local health authority.
    
              -  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. Note: Hepatitis B and Hepatitis C testing is not required unless
                 mandated by local health authority.
    
              -  Has active TB (Bacillus Tuberculosis) infection.
    
              -  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.
    
              -  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 study, starting with the screening visit through 120 days
                 after the last dose of trial treatment.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Disease Free Survival (DFS)
    Time Frame:Up to 3 years from time of randomization
    Safety Issue:
    Description:To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) that is between 1-4 cm in size, regardless of PD-L1 TPS score. Median Disease Free Survival (DFS) will be reported.

    Secondary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:Up to 3 years from time of randomization
    Safety Issue:
    Description:To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves overall survival compared with observation in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size, regardless of PD-L1 TPS. Median Overall Survival will be reported
    Measure:1 Year Disease Free Survival Rate
    Time Frame:Up to 1 year from time of randomization
    Safety Issue:
    Description:To evaluate the disease-free survival rate at 1 year on each arm.
    Measure:1 Year Overall Survival Rate
    Time Frame:Up to 1 year from time of randomization
    Safety Issue:
    Description:To evaluate the overall survival rate at 1 year on each arm.
    Measure:2 Year Disease Free Survival Rate
    Time Frame:Up to 2 years from time of randomization
    Safety Issue:
    Description:To evaluate the disease-free survival rate at 2 years on each arm.
    Measure:2 Year Overall Survival Rate
    Time Frame:Up to 2 years from time of randomization
    Safety Issue:
    Description:To evaluate the overall survival rate at 2 years on each arm.
    Measure:3 Year Disease Free Survival
    Time Frame:Up to 3 years from time of randomization
    Safety Issue:
    Description:To evaluate the disease-free survival rate at 3 years on each arm.
    Measure:3 Year Overall Survival Rate
    Time Frame:Up to 3 years from time of randomization
    Safety Issue:
    Description:To evaluate the overall survival rate at 3 years on each arm.
    Measure:Summarize Grade 3 & 4 Adverse Events
    Time Frame:Up to 3 years from time of randomization
    Safety Issue:
    Description:To characterize the toxicity profile of adjuvant Pembrolizumab following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Greg Durm, MD

    Last Updated

    March 19, 2020