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

NCT02955290 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: I 286816NCI-2016-01467
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 5

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.

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; Advanced Squamous Non-Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT) as graded by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v. 4.03) (Phase I)

  No formal analyses of DLTs are planned. Presentation of DLTs will be limited to DLT-evaluable patients.

  Up to 4 weeks (2 doses of study drugs)

• Overall survival (Phase II)

  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.

  At 12 months

• Progression-free survival (PFS) - Phase II

  Number of months between Loading Phase and documentation of disease progression, death or censoring, whichever occurs first.

  At 12 monts

Secondary Outcomes (3)

• Incidence of adverse events (AEs) graded according to National Cancer Institute version 4.03 (NCI CTCAE v4.03) (Phase I and II)

  Up to 120 days after the last dose of study treatment

• Progression free survival (PFS) based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) (Phase II)

  Up to 12 months

• Overall Survival (OS)

  UP to 12 months

Other Outcomes (3)

• Blood EGF levels, platelet levels, markers of immune response, and antibody functionality (Phase I and II)

  Up to 12 months from 5th vaccine dose

• EGFR and PD-1 expression and mutations in tumor tissue (Phase I and II)

  Up to 14 days after the last dose of CIMAvax

• 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)

  Up to 12 months

Study Arms (4)

Phase I (CIMAvax, nivolumab)

EXPERIMENTAL

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; Biological: Nivolumab; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Phase II Study A and B (CIMAvax, nivolumab)

EXPERIMENTAL

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; Biological: Nivolumab; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Phase II Study C, D & E (CIMAvax, pembrolizumab)

EXPERIMENTAL

PHASE II STUDY C, D \& E: 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 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Phase II Study D (CIMAvax, pembrolizumab)

EXPERIMENTAL

PHASE II STUDY D: Patients with PD-L1 expression \< 50% after 4 cycles of induction chemotherapy with pembrolizumab, receive CIMAvax IM and pembrolizumab IV over 30 minutes. Treatment repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Phase I (CIMAvax, nivolumab); Phase II Study A and B (CIMAvax, nivolumab); Phase II Study C, D & E (CIMAvax, pembrolizumab); Phase II Study D (CIMAvax, pembrolizumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Phase I (CIMAvax, nivolumab); Phase II Study A and B (CIMAvax, nivolumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Phase II Study C, D & E (CIMAvax, pembrolizumab); Phase II Study D (CIMAvax, pembrolizumab)

Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine BIOLOGICAL

Given CIMAvax IM

Also known as: 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

Phase I (CIMAvax, nivolumab); Phase II Study A and B (CIMAvax, nivolumab); Phase II Study C, D & E (CIMAvax, pembrolizumab); Phase II Study D (CIMAvax, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at the time of study treatment initiation
• Have pathologically confirmed diagnosis of NSCLC (Phase I, Phase II Studies A, C and D, E and Expansion Cohort) 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 unresectable NSCLC with PD-L1 expression \>= 50% for first line therapy in advanced stage. 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
• Phase II Study D: Patients with advanced squamous NSCLC with PD-L1 expression \<50% with PR/CR or stable disease by RECIST after at least 4 cycles of induction chemoimmunotherapy with platinum-based combination with pembrolizumab, prior to initiation of maintenance pembrolizumab
• Phase II Study E: Patients with advanced NON-Squamous NSCLC (without EGFR/ALK/ROS-1/KRAS mutations) with PD-L1 expression \<50% with PR/CR or stable disease by RECIST after at least 4 cycles of induction chemoimmunotherapy with platinum-based combination with pembrolizumab, prior to initiation of maintenance pembrolizumab
• 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 /plasma 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)

You may not qualify if:

• Receipt of anticancer chemotherapy within 4 weeks before the first administration of study drug
• Previous anti-PD1 or PD-L1 immunotherapy is not allowed;(exceptions: cohort D, E and expansion cohort). Treatment with other investigational agents within 6 half-lives of first administration of study drug is not allowed
• 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
• Have an active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease-modifying antirheumatic agents or immunosuppressive drugs) Note: Replacement therapy (e.g. thyroxine, insulin as replacement therapy for thyroid, diabetes) is permitted.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 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) within 6 months prior to baseline

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (5)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

Good Samaritan Hospital

West Islip, New York, 11795, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Lung Neoplasms

Interventions

Nivolumab; pembrolizumab; CIMAvax EGF

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Prantesh Jain, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 4, 2016
• Study Start: December 22, 2016
• Primary Completion: May 23, 2025
• Study Completion (Estimated): December 9, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (5)