Clinical Trials /

Nimotuzumab and Nivolumab in Treating Patients With Advanced Non-small Cell Lung Cancer

NCT02947386

Description:

This phase I/II trial studies the best dose and side effects of nimotuzumab when giving together with nivolumab and to see how well they work in treating patients with non-small cell lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Monoclonal antibodies, such as nimotuzumab and nivolumab, may block tumor growth in different ways by targeting certain cells.

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

Suspended

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nimotuzumab and Nivolumab in Treating Patients With Advanced Non-small Cell Lung Cancer
  • Official Title: A Phase I/II Open-Label Study of Nimotuzumab in Combination With Nivolumab in Patients With Advanced Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: I 281616
  • SECONDARY ID: NCI-2016-01476
  • SECONDARY ID: I 281616
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT02947386

Conditions

  • EGFR Gene Mutation
  • Recurrent Non-Small Cell Lung Carcinoma
  • Stage IIIA Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
NimotuzumabThera-CIM-hr3, TheraCim hR3, TheralocTreatment (nivolumab, nimotuzumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab, nimotuzumab)

Purpose

This phase I/II trial studies the best dose and side effects of nimotuzumab when giving together with nivolumab and to see how well they work in treating patients with non-small cell lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Monoclonal antibodies, such as nimotuzumab and nivolumab, may block tumor growth in different ways by targeting certain cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the dose-limiting toxicities (DLT) and estimate the maximum tolerated dose
      (MTD) of nimotuzumab combined with nivolumab in the therapy of advanced non-small cell lung
      cancer (NSCLC) in order to establish the recommended phase II dose (RP2D). (Phase I)

      II. To evaluate the 12 month overall survival of nimotuzumab in combination with nivolumab in
      patients with advanced NSCLC. (Phase II)

      SECONDARY OBJECTIVES:

      I. Examine the safety and tolerability profile of nivolumab in combination with nimotuzumab
      in NCSLC . (Phase I)

      II. To evaluate the safety and the tolerability of nimotuzumab in combination with nivolumab
      using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common
      Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase I)

      III. Determine the immune analysis profile of nivolumab in combination with nimotuzumab.
      (Phase I)

      IV. Examine the efficacy of the study combination utilizing irRECIST guidelines. (Phase I)

      V. Overall response rate (ORR) per the immune-related Response Evaluation Criteria in Solid
      Tumors irRECIST. (Phase I)

      VI. Progression-free survival (PFS) rate at 1 year. (Phase I)

      VII. Progression-free survival (PFS). (Phase I)

      VIII. Overall survival (OS). (Phase I)

      IX. Disease control rate (DCR) and stable disease (SD). (Phase I)

      X. To evaluate the safety profile of Nimotuzaumab in combination with Nivolumab in NCSLC
      using the CTCAE V. 4.

      XI.To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with
      advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary
      measures of efficacy, including: overall response rate (ORR) per irRECIST. (Phase II)

      XII. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with
      advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary
      measures of efficacy, including: progression-free survival (PFS) rate at 1 year. (Phase II)

      XIII. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with
      advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary
      measures of efficacy, including: progression-free survival (PFS). (Phase II)

      XIV. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with
      advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary
      measures of efficacy, including: overall survival (OS). (Phase II)

      XV. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with
      advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary
      measures of efficacy, including: disease control rate (DCR) and stable disease (SD). (Phase
      II)

      TERTIARY OBJECTIVES:

      I. Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and adverse events
      (AE). (Phase I)

      II. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and
      genetic markers, and their associated PD-1, CD45RA or CD45RO levels; PD-L1 expression within
      both neoplastic and non-neoplastic stromal elements of the tumor microenvironment to PFS, OS,
      ORR and AE. (Phase I)

      III. Comparison of response assessment criteria for a prospective analysis; irRECIST response
      assessment; irRC. (Phase I)

      IV. Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and AE. (Phase II)

      V. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and
      genetic markers, and their associated PD-1, CD45RA or CD45RO levels. (Phase II)

      VI. Examine the relationship of PD-L1 expression within both neoplastic and non-neoplastic
      stromal elements of the tumor microenvironment to PFS, OS, ORR and AE. (Phase II)

      VII. Comparison of response assessment criteria for a prospective analysis; irRECIST response
      assessment; irRC. (Phase II)

      OUTLINE: This is a phase I, dose-escalation study of nimotuzumab followed by a phase II
      study.

      Patients receive nivolumab intravenously (IV) over 60 minutes and nimotuzumab IV over 60
      minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 12
      weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, nimotuzumab)ExperimentalPatients receive nivolumab IV over 60 minutes and nimotuzumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Nimotuzumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Patients with pathologically confirmed non-small cell lung cancer

          -  Patients must have had progressive NSCLC after first-line platinum-based chemotherapy
             for advanced disease

          -  Have at least 3 months life expectancy

          -  Have measurable disease per RECIST 1.1 criteria present

          -  Patients with adenocarcinoma known to have anaplastic lymphoma kinase (ALK)
             rearrangements and/or epidermal growth factor receptor (EGFR) mutations that have had
             prior EGFR or ALK tyrosine kinase inhibitor therapy and have progressed, will also be
             eligible, regardless of line of therapy

          -  Phase I optional archival tissue/phase II mandatory archival tissue: able to provide
             enough biopsy tissue samples including primary diagnostic biopsy (archival), re-biopsy
             tissues (archival from time of disease progression/recurrence following first-line
             treatment failure) at disease progression to determine PD-L1 and EGFR expression and
             other biomarkers

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Hemoglobin >= 9 g/dL

          -  Serum creatinine =< 1.5 x institution upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 x ULN or =<
             5 x ULN if liver metastases are present

          -  Total serum bilirubin =< ULN; or total bilirubin =< 3.0 x ULN with direct bilirubin
             within normal range in patients with well documented Gilbert's syndrome

          -  Troponin-I, CK-MB, BNP <= ULN

          -  LVEF >= LLN

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry; 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

          -  Participant or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent form prior to receiving any study related procedure

        Exclusion Criteria:

          -  Active autoimmune disease that has required systemic treatment in past 2 years; use of
             inhaled corticosteroids is allowed

          -  Phase II only: history of other malignancies are allowed as long as the current
             disease stage that did not require active treatment with concomitant systemic
             cytotoxic chemotherapy, targeted therapy, investigational or biologic therapy (e.g.,
             anti-CTLA4 or HER2 monoclonal antibodies) within 12 months prior to study registration
             and, is not likely to require systemic therapy in the next 12 months; hormone-related
             therapies (e.g., somatostatin analogues, etc.) are allowed on a case-to-case basis
             upon discussion with principal investigator

          -  Active clinically serious infections requiring antibiotics, antiviral or antifungal
             agents; participants must be off these agents for at least 28 days prior to the first
             dose of the study drug

          -  Symptomatic brain metastases; uncontrolled pleural effusion, seroperitoneum, or
             pericardial effusion

          -  Has had any major surgery, chemotherapy, or radiotherapy within the previous 4 weeks;
             gamma knife radiosurgery for brain metastases within less than 2 weeks

          -  Receiving other anti-cancer medical treatment during the study outside of the
             nimotuzumab or nivolumab

          -  Clinically significant interstitial pulmonary disease or known diagnosis of
             interstitial lung disease (ILD)

          -  Has known immunosuppressive disease (e.g. human immunodeficiency virus [HIV], acquired
             immune deficiency syndrome [AIDS])

          -  Patient has known hypersensitivity to the components of the study drugs or their
             analogs

          -  Patient with uncontrolled cardiac disease or cardiac dysfunction, including any of the
             following:

               -  History of uncontrolled angina pectoris that does not respond to medical
                  intervention

               -  Symptomatic pericarditis or myocardial infarction within 12 months prior to study
                  entry that did not respond to treatment

               -  History of documented congestive heart failure (New York Heart Association
                  functional classification III or IV)

               -  Documented cardiomyopathy

               -  Uncontrolled hypertension defined by: systolic blood pressure (SBP) >= 160 mmHg
                  and/or diastolic blood pressure (DBP) >= 100 mmHg

          -  Pregnant or nursing female participants

          -  Unwilling or unable to follow protocol requirements

          -  Any condition which in the investigator's opinion deems the participant an unsuitable
             candidate to receive study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:DLT as graded by NCI CTCAE version 4.0 (Phase I)
Time Frame:Up to 28 days
Safety Issue:
Description:No formal analyses of DLTs are planned. Participants who do not have a DLT and who do not complete a full cycle of treatment will be considered non-evaluable for DLT.

Secondary Outcome Measures

Measure:Incidence of adverse events assessed by NCI CTCAE version 4.0 (Phase I and II)
Time Frame:Up to 30 days after the last dose of study treatment
Safety Issue:
Description:The frequency of AEs will be tabulated by grade across all dose levels and cycles. All patients who receive any study treatment will be considered evaluable for toxicity.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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