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

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 242

Inclusion Criteria

Inclusion Criteria: - 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) - 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 =< ULN and 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. Patients enrolled onto Phase II D or E must have measurable disease as defined in RECIST 1.1 prior to induction chemmoimmunotherapy. - 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 and Cohort D or E (i.e.; fresh biopsy is NOT mandatory). 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;(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

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicity (DLT) as graded by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v. 4.03) (Phase I);Overall survival (Phase II);Progression-free survival (PFS) - Phase II

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs) graded according to National Cancer Institute version 4.03 (NCI CTCAE v4.03) (Phase I and II);Progression free survival (PFS) based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) (Phase II);Overall Survival (OS)

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