Nimotuzumab and Nivolumab in Treating Patients with Advanced Non-small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Patients with pathologically proven non-small cell lung cancer squamous head and neck cancer
• Patient must be a candidate for nivolumab as standard of care regardless of line of therapy
• Have at least 6 months life expectancy
• Phase I: Must have evaluable disease present. Phase II: Must have measurable disease per RECIST 1.1 criteria present
• Patients with advanced (metastatic) NSCLC or squamous cell head and neck cancer, whose disease progressed during or after platinum-based chemotherapy; patients with EGFR or ALK genomic tumor aberrations (testing required for adenocarcinoma patients) should have disease progression on Food and Drug Administration (FDA)-approved therapy for these aberrations prior to receiving Nivolumab; these patients are eligible regardless of line of therapy
• Phase I/II archived tissue collection: will be requested when available, but is not mandatory for inclusion
• Phase II mandatory pre-treatment and post-treatment fresh biopsies 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) =< 3 x ULN or =< 5 x ULN if liver metastases are present
• Total serum bilirubin =< 1.5 x ULN; or total bilirubin =< 3 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s syndrome
• Troponin-I, creatine kinase MB (CK-MB) =< ULN, B-type natiuretic peptide (BNP) < 200 pg/ml
• Left ventricular ejection fraction (LVEF) >= lower limit of normal (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

• History of autoimmune disorder with exception of eligible patients with vitiligo or endocrine-related autoimmune conditions receiving appropriate hormonal supplementation. Use of immunosuppressant drugs such as steroids (except as hormone replacement therapy or as supportive medication e.g. anti-emesis, contrast allergy, premedication, etc. or other short-course therapy less than 2 weeks continuously within 4 weeks of study treatment), azathioprine, tacrolimus, cyclosporine, etc. is not permitted within 4 weeks before recruitment
• Phase II portion 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 =< 6 (under surveillance or treated)
• Active clinically serious infections requiring antibiotics, antiviral or antifungal agents
• 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
• Has had any 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
• Receipt of anticancer chemotherapy, immunotherapy and/or anti-EGFR antibody within 4 weeks before the first administration of study drug; patients who received anti-EGFR antibody in combination with anti-PD1/anti-PD-L1 immunotherapy are excluded regardless of time interval from last drug administration
• History of CTC grade 2 or higher immune-related adverse event to anti-PD1/PD-L1 (exceptions allowed: endocrine disorder controlled on hormone replacement or pruritus/rash or other dermatologic AEs not requiring systemic steroids)
• Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug for management of brain metastases or immune-related adverse event, or who have not fully recovered from side effects of such treatment (steroids for endocrine replacement or use as supportive medication such as anti-emesis, contrast allergy, pre-medication, etc. or other short-course therapy less than 2 weeks continuously within 4 weeks of study treatment are allowed exceptions)
• Clinically significant interstitial pulmonary disease or known diagnosis of interstitial lung disease (ILD)
• Has known immunodeficiency disease (e.g. human immunodeficiency virus [HIV], acquired immunodeficiency syndrome [AIDS]); has known hepatitis B or C; testing is not mandatory
• Received a live vaccine within 30 days of first protocol treatment
• Patient has known hypersensitivity to the components of the study drugs or their 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 defined by: systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood Pressure (DBP) > 100 mmHg * History of myocarditis of any etiology * History of cardiac surgery * History of ventricular arrhythmias
• 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
• Patients requiring 24-hour continuous oxygen therapy
• Tumor with mutation that is known to be sensitive to FDA approved targeted therapy but has not yet received such therapy
• Phase II patients only: Patients who have ongoing complete response (CR) or partial response (PR), or unknown response status, with immunotherapy * Note: Patients with disease progression on immunotherapy, even if PR or CR was previously documented, will be eligible.)