Clinical Trials /

CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer

NCT02955290

Description:

This phase I/II trial studies the best dose and side effects of recombinant human EGF-rP64K/montanide ISA 51 vaccine (CIMAvax) and nivolumab and to see how well they work in treating patients with non-small cell lung cancer or squamous head and neck cancer that has spread to other places in the body. Vaccine therapy, such as CIMAvax vaccine may help slow down and stop tumor growth. Immunotherapy with monoclonal antibodies, such as nivolumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CIMAvax vaccine together with nivolumab or pembrolizumab may work better in treating patients with non-small cell lung cancer or squamous head and neck cancer.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer
  • Official Title: A Phase I/II Basket Trial of the EGF Vaccine CIMAvax in Combination With Anti-PD1 Therapy in Patients With Advanced NSCLC or Squamous Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: I 286816
  • SECONDARY ID: NCI-2016-01467
  • SECONDARY ID: I 286816
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT02955290

Conditions

  • Advanced Head and Neck Squamous Cell Carcinoma
  • Lung Non-Small Cell Carcinoma
  • Metastatic Lung Non-Small Cell Carcinoma
  • PD-L1 Positive
  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
  • Stage III Lung Cancer AJCC v8
  • Stage IIIA Lung Cancer AJCC v8
  • Stage IIIB Lung Cancer AJCC v8
  • Stage IIIC Lung Cancer AJCC v8
  • Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8
  • Unresectable Lung Non-Small Cell Carcinoma

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoPhase I (CIMAvax, nivolumab)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Phase II Study C (CIMAvax, pembrolizumab)
Recombinant Human EGF-rP64K/Montanide ISA 51 VaccineCenter of Molecular Immunology (CIMA) Epidermal Growth Factor (EGF) Vaccine, Center of Molecular Immunology Epidermal Growth Factor Vaccine, Cimavax, CIMAvax EGF, CIMAvax Epidermal Growth Factor Vaccine, CIMAvax-EGF, Recombinant Human EGF-P64K/Montanide VaccinePhase I (CIMAvax, nivolumab)

Purpose

This phase I/II trial studies the best dose and side effects of recombinant human EGF-rP64K/montanide ISA 51 vaccine (CIMAvax) and nivolumab and to see how well they work in treating patients with non-small cell lung cancer or squamous head and neck cancer that has spread to other places in the body. Vaccine therapy, such as CIMAvax vaccine may help slow down and stop tumor growth. Immunotherapy with monoclonal antibodies, such as nivolumab and pembrolizumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CIMAvax vaccine together with nivolumab or pembrolizumab may work better in treating patients with non-small cell lung cancer or squamous head and neck cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To identify the maximum dose of CIMAvax in combination with nivolumab based on dose
      limiting toxicities (DLTs) as assessed by Common Terminology Criteria for Adverse Events
      version 4.03 (CTCAE version [v] 4.03). (Phase I) II. To evaluate the 12-month overall
      survival of CIMAvax combined with nivolumab in patients with advanced non-small cell lung
      cancer (NSCLC). (Phase II-Study A) III. To evaluate the 6-month progression free survival
      (PFS) of CIMAvax combined with nivolumab in patients with advanced recurrent squamous cell
      carcinoma of the head and neck. (Phase II-Study B) IV. To evaluate the objective response
      rate of pembrolizumab in combination with CIMAvax as first-line therapy in patients with
      advanced NSCLC (PD-L1 expression >= 50%). (Phase II-Study C)

      SECONDARY OBJECTIVES I. To assess the toxicity of CIMAvax combined with nivolumab using the
      Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology
      Criteria for Adverse Events (CTCAE version 4.03). (Phase I) II. Determine the preliminary
      efficacy of the combination of anti-PD1 therapy with CIMAvax. (Phase I) III. To evaluate
      progression free survival (PFS) for the combination of CIMAvax and nivolumab in patients with
      advanced NSCLC. (Phase II-Study A) IV. To evaluate the 12-month overall survival of patients
      with advanced recurrent squamous cell carcinoma of the head and neck who received nivolumab
      in combination with CIMAvax. (Phase II-Study B) V. To evaluate the PFS and 12-month overall
      survival of CIMAvax in combination with pembrolizumab as first-line therapy in patients with
      advanced NSCLC (PD-L1 expression >= 50%). (Phase II-Study C) VI. To assess the toxicity of
      CIMAvax combined with nivolumab using the CTEP NCI Common Terminology Criteria for Adverse
      Events (CTCAE version 4.03). (Phase II)

      TERTIARY OBJECTIVES:

      I. To conduct correlative studies comparing blood EGF levels, platelet levels, markers of
      immune response and functionality of antibody response. (Phase I) II. To examine the
      association of EGFR (total and activated), PD-1 and PD-L1 expression and mutations in tumor
      tissue with biomarkers of genetic and immune response. (Phase I and II) III. Comparison of
      response assessment criteria for a prospective analysis (immune-related [ir] Response
      Evaluation Criteria in Solid Tumors [RECIST] response assessment versus [vs.] immune-related
      Response Criteria [irRC] vs. RECIST 1.1). (Phase I and II) IV. To characterize the blood EGF
      levels and other blood-based biomarkers of patients censored from the trial because of low
      titer response. (Phase II)

      OUTLINE: This is a phase I dose escalation study of CIMAvax followed by a phase II study.

      LOADING PHASE I: Patients receive CIMAvax intramuscularly (IM) and nivolumab intravenously
      (IV) over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 doses in the
      absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose,
      patients receive CIMAvax IM at the same time as the next nivolumab dose.

      MAINTENANCE PHASE I: Patients who do not experience a DLT receive CIMAvax every 4 weeks and
      nivolumab every 2 weeks.

      PHASE II STUDY A and B: Patients receive CIMAvax IM and nivolumab IV over 60 minutes.
      Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4
      weeks during the maintenance phase in the absence of disease progression or unacceptable
      toxicity. Courses for nivolumab repeat every 2 weeks in the absence of disease progression or
      unacceptable toxicity. Patients in Study A with antibody titer >= 1:4000 at the end of the
      loading phase may receive CIMAvax IM every 8 or 12 weeks during the maintenance phase.

      PHASE II STUDY C: Patients with PD-L1expression >= 50% receive CIMAvax IM and pembrolizumab
      IV over 30 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the
      loading phase and every 4 weeks during the maintenance phase in the absence of disease
      progression or unacceptable toxicity. Courses for pembrolizumab repeat every 2 weeks for 2
      years in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 30 days for 120 days.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I (CIMAvax, nivolumab)ExperimentalLOADING PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose. MAINTENANCE PHASE I: Patients who do not experience a DLT receive CIMAvax every 4 weeks and nivolumab every 2 weeks.
  • Nivolumab
  • Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Phase II Study A and B (CIMAvax, nivolumab)ExperimentalPHASE II STUDY A and B: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4 weeks during the maintenance phase in the absence of disease progression or unacceptable toxicity. Courses for nivolumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients in Study A with antibody titer >= 1:4000 at the end of the loading phase may receive CIMAvax IM every 8 or 12 weeks during the maintenance phase.
  • Nivolumab
  • Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Phase II Study C (CIMAvax, pembrolizumab)ExperimentalPHASE II STUDY C: Patients with PD-L1 expression >= 50% receive CIMAvax IM and pembrolizumab IV over 30 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4 weeks during the maintenance phase in the absence of disease progression or unacceptable toxicity. Courses for pembrolizumab repeat every 2 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
  • Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Eligibility Criteria

        Inclusion Criteria:

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 at the
             time of study treatment initiation

          -  Have pathologically confirmed diagnosis of NSCLC (Phase I, Phase II Studies A, C and
             Expansion Cohort AE) or squamous cell head and neck cancer (Phase II Study B)

          -  Must be eligible for treatment with nivolumab as standard of care (for nivolumab
             treatment groups only)

          -  Phase II Study A and Expansion Cohort AE: Patients with advanced (metastatic) NSCLC,
             whose disease progressed during or after platinum based therapy

          -  Phase II Study B: Patients with advanced recurrent head and neck squamous cell
             carcinoma

          -  Phase II Study C: Patients with advanced unresectable NSCLC, first-line therapy with
             PD-L1 expression >= 50%; in the rare event that there is a discrepancy in the results
             of PD-L1 testing (i.e. 2 or more specimens were tested, etc.), eligibility status will
             be per the discretion of the principal investigator (PI) after review of other
             available biomarker testing

          -  NSCLC patients in study A and expansion cohort AE with EGFR or ALK genomic tumor
             aberrations (determined through either tissue- or liquid biopsy-based platform) should
             have disease progression on Food and Drug administration (FDA)-approved therapy for
             these aberrations prior to receiving nivolumabanti-PD1 therapy; patients with smoking
             history being considered for Study C may enroll and be treated pending results of
             molecular testing

          -  Have at least 6 month life expectancy

          -  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) or estimated
             glomerular filtration rate (GFR) (measured or calculated with Cockcroft and Gault
             formula) > 45 ml/min

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (ALT
             and AST =< 5 x ULN is acceptable if liver metastases are present)

          -  Total serum bilirubin =< 1.5 x ULN; for patients with well documented Gilbert?s
             syndrome, total bilirubin =< 3 x ULN with direct bilirubin within normal range

          -  Troponin-I, creatine kinase muscle and brain (CK-MB) =< ULN, B-type natriuretic
             peptide (BNP) < 200 pg/ml

          -  Left ventricular ejection fraction (LVEF) >= lower limit of normal (LLN)
             (institutional limit)

          -  Patients enrolled onto Phase I dose escalation or Expansion Cohort (AE) must have
             presence of evaluable disease; patients enrolled onto Phase II studies A, B, or C must
             have measurable disease as defined in RECIST 1.1

          -  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

          -  Phase II studies: Participant agrees to provide tumor biopsy tissue before treatment,
             blood samples at the start of treatment and at multiple times during the study and, a
             tumor biopsy at the end of the trial or after disease progression; archival
             formalin-fixed paraffin-embedded (FFPE) tissue is permitted for Expansion Cohort AE;
             archival FFPE tissue is also permitted for Study C patients provided that tissue is
             adequate and no systemic anti-cancer therapy had been administered between the time
             specimen was obtained and start of protocol therapy

        Exclusion Criteria:

          -  Receipt of anticancer chemotherapy within 4 weeks before the first administration of
             study drug

          -  Previous anti-PD1 or PD-L1 immunotherapy is not allowed; treatment with other
             investigational agents within 6 half-lives of first administration of study drug is
             not allowed

          -  Patients requiring 24-hour continuous oxygen therapy

          -  Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain
             metastasis; subjects must have recovered from all radiation related toxicities

          -  Active/untreated brain metastasis; whole brain radiation or gamma knife radiosurgery
             performed less than 4 weeks prior to first administration of study drug; previously
             treated brain metastasis allowed as long as not requiring steroids and stable on
             imaging at least 4 weeks after completing radiation therapy

          -  Leptomeningeal involvement regardless of treatment status

          -  Tumor with mutation that is known to be sensitive to FDA approved targeted therapy but
             has not yet received such targeted therapy

          -  History of autoimmune disorder, with exception of patients with vitiligo or
             endocrine-related autoimmune conditions receiving appropriate hormonal supplementation
             who are eligible; systemic use of immunosuppressant drugs such as steroids (except as
             hormone replacement therapy or short-course supportive medication such as chemotherapy
             or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc. within 4 weeks
             before recruitment

          -  Currently receiving or has received systemic corticosteroids within 4 weeks prior to
             starting study drug for management of brain metastases, or who have not fully
             recovered from side effects of such treatment; steroids for endocrine replacement or
             receipt of short-course of steroids during the preceding 4 week period as supportive
             medication such as for drug allergy, anti-emetic, etc. is allowed

          -  Had major surgery within 14 days prior to starting study drug or has not recovered
             from major side effects (tumor biopsy is not considered major surgery) resulting from
             a prior surgery

          -  Has known immunosuppressive disease (e.g. human immunodeficiency virus [HIV], acquired
             immune deficiency syndrome [AIDS] or other immune depressing disease); testing is not
             mandatory

          -  Active, clinically serious infections or other serious uncontrolled medical conditions

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

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study, interfere with the patient?s participation
             for the full duration of the study, or is not in the best interest of the patient to
             participate, in the opinion of the treating investigator, including, but not limited
             to:

               -  Myocardial infarction or arterial or venous thromboembolic events within 6 months
                  prior to baseline or severe or unstable angina, New York Heart Association (NYHA)
                  class III or IV disease

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

               -  Documented history of cardiomyopathy

               -  Uncontrolled hypertension (systolic blood pressure [SBP] > 160/diastolic blood
                  pressure [DBP] > 100 despite medical intervention)

               -  History of myocarditis of any etiology

               -  History of cardiac surgery

               -  History of ventricular arrhythmias

          -  Phase II only: Patients diagnosed with an invasive cancer within 2 years prior to
             starting protocol therapy with the following exceptions: non-melanoma skin cancers,
             in-situ cancers, and prostate cancer gleason =< to 6 (under surveillance or treated),
             early stage node-negative estrogen receptor (ER)+/progesterone receptor (PR)+ breast
             cancer with Oncotype Dx score < 25 not taking adjuvant hormonal therapy

          -  Pregnant or nursing female participants

          -  Any condition which in the investigator?s opinion deems the participant an unsuitable
             candidate to receive study drug

          -  Unwilling or unable to follow protocol requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity (DLT) as graded by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v. 4.03) (Phase I)
Time Frame:Up to 4 weeks (2 doses of study drugs)
Safety Issue:
Description:No formal analyses of DLTs are planned. Presentation of DLTs will be limited to DLT-evaluable patients.

Secondary Outcome Measures

Measure:Incidence of adverse events (AEs) graded according to National Cancer Institute version 4.03 (NCI CTCAE v4.03) (Phase I and II)
Time Frame:Up to 30 days after the last dose of study treatment
Safety Issue:
Description:The maximum grade for each type of AEs will be recorded for each patient based on NCI CTCAE version 4.0. The frequency of AEs will be tabulated by maximum grade per event across all dose levels and cycles. All patients who receive any study treatment will be considered evaluable for toxicity.
Measure:Progression free survival (PFS) based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) (Phase II)
Time Frame:Up to 12 months
Safety Issue:
Description:PFS will be defined as the number of months between Loading Phase enrollment and documentation of disease progression or death, whichever is observed first. PFS will be presented using Kaplan-Meier plots and associated statistics.

Details

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

Last Updated