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

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ClinicalTrials.gov Identifier: NCT02955290
Recruitment Status : Recruiting
First Posted : November 4, 2016
Last Update Posted : March 26, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Other: Laboratory Biomarker Analysis Biological: Nivolumab Biological: Pembrolizumab Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 181 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 22, 2016
Estimated Primary Completion Date : June 9, 2020
Study Completion Date : June 9, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase I (CIMAvax, nivolumab)

LOADING 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.

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given CIMAvax IM
Other Names:
  • Center 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 Vaccine

Experimental: Phase II Study A and B (CIMAvax, nivolumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given CIMAvax IM
Other Names:
  • Center 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 Vaccine

Experimental: Phase II Study C (CIMAvax, pembrolizumab)
PHASE 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given CIMAvax IM
Other Names:
  • Center 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 Vaccine




Primary Outcome Measures :
  1. 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) ]
    No formal analyses of DLTs are planned. Presentation of DLTs will be limited to DLT-evaluable patients.

  2. Overall survival (Phase II) [ Time Frame: At 12 months ]
    Overall survival will be defined as the number of months between Loading Phase enrollment and death from any cause. Overall survival will be presented using Kaplan-Meier plots and associated statistics.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Progression free survival (PFS) based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) (Phase II) [ Time Frame: Up to 12 months ]
    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.


Other Outcome Measures:
  1. Blood EGF levels, platelet levels, markers of immune response, and antibody functionality (Phase I and II) [ Time Frame: Up to 12 months from 5th vaccine dose ]
    Blood EGF levels, platelet levels, and biomarkers of immune response will be reported using appropriate descriptive statistics. Associations between these measures will be explored in the overall sample using the correlation coefficients.

  2. EGFR and PD-1 expression and mutations in tumor tissue (Phase I and II) [ Time Frame: Up to 14 days after the last dose of CIMAvax ]
    EGFR and PD-1 expression and mutations in tumor tissue will be reported using appropriate descriptive statistics. The association between these measures and the biomarkers of immune response will be evaluated using general linear models.

  3. Response assessed using irRECIST, immune-related Response Criteria (irRC), and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase I and II) [ Time Frame: Up to 12 months ]
    Response assessment criteria will be compared between irRECIST, irRC, and RECIST 1.1 for a prospective analysis.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955290


Locations
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United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Grace K. Dy    716-845-3099    Grace.Dy@RoswellPark.org   
Principal Investigator: Grace K. Dy         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Grace Dy Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT02955290     History of Changes
Other Study ID Numbers: I 286816
NCI-2016-01467 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 286816 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Vaccines
Pembrolizumab
Nivolumab
Mitogens
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action