iC9-CAR.CSPG4 T-Cells for the Treatment of Patients with Recurrent or Refractory Head and Neck Squamous Cell Carcinoma

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject; subject given a copy of the informed consent form
• Age ≥ 18 years at the time of consent
• Karnofsky score of > 60%
• Histologically or cytologically confirmed stage recurrent/metastatic squamous cell carcinoma of the head and neck as defined by American Joint Committee on Cancer (AJCC). This typically includes squamous cancer of: oral cavity, oropharynx, hypopharynx and larynx. Nasopharyngeal cancer patients will eligible if clearly squamous and if Epstein-Barr virus negative (EBV-). Clearly squamous skull base tumors will be eligible. Squamous head and neck cancer of unknown site of origin will be eligible. Squamous skin cancers of the head/neck and non-squamous tumors will not be eligible. The use of historical pathology reports is acceptable for enrollment
• Subject must not have any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. * Subjects with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician * Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with study medications may be included only after consultation with the study physician
• Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 3 months after the cell infusion therapy
• Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
• Subject is willing to undergo a biopsy prior to treatment, after CAR T cell infusion and at the time of disease progression and the tumor is determined to be safe by the treating investigator for biopsy collection and the procedure would not be required to be performed in the operating room
• Subject has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• PRIOR TO PROCUREMENT: Written informed consent to undergo cell procurement explained to, understood by and signed by the subject
• PRIOR TO PROCUREMENT: Subject has life expectancy of ≥ 12 weeks
• PRIOR TO PROCUREMENT: Subjects must be platinum refractory and have either progressed on a PD-1/PD-L1 inhibitor or are intolerant to receiving a PD-1/PD-L1 inhibitor
• PRIOR TO PROCUREMENT: All ≥ grade 3 adverse events (AEs )related to prior surgery, chemotherapy, radiation or disease should be resolved to grade 2
• PRIOR TO PROCUREMENT: Any opportunistic or active systemic infection should be resolved prior to lymphodepletion
• PRIOR TO PROCUREMENT: Subject must not have any unresolved toxicity NCI CTCAE grade ≥ 2 with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria * Subjects with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician * Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with study medications may be included only after consultation with the study physician
• PRIOR TO PROCUREMENT: Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
• PRIOR TO PROCUREMENT: Subject must have no history or current severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, uncontrolled arrhythmia, or myocardial infarction in the past 6 months
• PRIOR TO PROCUREMENT: Subject must have no history of stroke or transient ischemic attack (TIA) within 12 months before procurement
• PRIOR TO PROCUREMENT: Subject must have no history of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
• PRIOR TO PROCUREMENT: Subject must have no presence of any in-dwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter)
• PRIOR TO PROCUREMENT: Hemoglobin (Hgb) ≥ 8 g/dL at least 1 week following last transfusion (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Absolute neutrophil count (ANC) ≥ 1.0 X 10^9/L (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Platelets ≥ 100 X 10^9/L (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Creatinine ≤ 2 X upper limit of normal (ULN) (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Bilirubin ≤ 1.5 X upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 1.5 milligrams/deciliter (mg/dL) if their conjugated bilirubin is < 1.5 X ULN (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Aspartate aminotransferase (AST) ≤ 3 X ULN (≤ 5 X ULN if liver metastases present) (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Alanine aminotransferase (ALT) ≤ 3 X ULN ( ≤ 5 X ULN if liver metastases present) (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Pulse oximetry ≥ 90% on room air (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Subjects should not have undergone treatment with definitive radiation therapy within the last 3 months or treatment with short course palliative radiation therapy within the previous 2 weeks
• PRIOR TO PROCUREMENT: Current use of systemic corticosteroids at doses ≥ 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed. Physiologic replacement hydrocortisone at doses 6-12 mg/m^2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10 mg prednisone per day
• PRIOR TO PROCUREMENT: Active infection with HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for hepatitis B surface antigen, negative for HCV antibody or HCV viral load
• PRIOR TO LYMPHODEPLETION: Written informed consent to undergo therapy with iC9-CAR.CSPG4 T cells explained to, understood by and signed by the subject; subject given a copy of informed consent form
• PRIOR TO LYMPHODEPLETION: No major surgery within 28 days to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject has not received any investigational agents or any tumor vaccines within 6 weeks prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject must have no history or current severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, uncontrolled arrhythmia, or myocardial infarction in the past 6 months
• PRIOR TO LYMPHODEPLETION: Subject must have no history of stroke or transient ischemic attack (TIA) within 12 months before procurement
• PRIOR TO LYMPHODEPLETION: Subject must have no history of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
• PRIOR TO LYMPHODEPLETION: Subject must have no presence of any in-dwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter)
• PRIOR TO LYMPHODEPLETION: Subject has not received chemotherapy or radiation therapy within the previous 3 weeks prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: All ≥ grade 3 AEs related to prior surgery, radiation or disease should be resolved to grade 2 prior to lymphodepletion. AEs should be ≤ 2 in order to repeat lymphodepletion
• PRIOR TO LYMPHODEPLETION: Any opportunistic or active systemic infection should be resolved prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject using systemic corticosteroids at doses ≥ 10 mg prednisone daily or its equivalent will be excluded; those receiving < 10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed. Physiologic replacement hydrocortisone at doses 6-12 mg/m^2/day is allowed. Equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10 mg prednisone per day
• PRIOR TO LYMPHODEPLETION: Imaging results from within 7 days prior to lymphodepletion to confirm the presence of measurable disease per RECIST 1.1. Imaging must occur at least 3 weeks after most recent therapy, including any bridging therapy (used as baseline and to document measurable disease)
• PRIOR TO LYMPHODEPLETION: Subject must have available iC9-CAR.CSPG4 T cells that meet the Certificate of Analysis acceptance criteria
• PRIOR TO LYMPHODEPLETION: Hemoglobin (Hgb) ≥ 8 g/dL at least 1 week following last transfusion (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Absolute neutrophil count (ANC) ≥ 1.0 X 10^9/L (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Platelets ≥ 100 X 10^9/L (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Creatinine ≤ 2 X ULN (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Bilirubin ≤ 1.5 X upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 1.5 milligrams/deciliter (mg/dL) if their conjugated bilirubin is < 1.5 X ULN (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Aspartate aminotransferase (AST) ≤ 3 X ULN ( ≤ 5 X ULN if liver metastases present) (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Alanine aminotransferase ≤ 3 X ULN ( ≤ 5 X ULN if liver metastases present) (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for female participants of childbearing potential. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• PRIOR TO LYMPHODEPLETION: Subject does not have rapidly progressive disease, per treating oncologist’s discretion
• PRIOR TO LYMPHODEPLETION: Subject is a good candidate for CAR T cell therapy, per treating oncologist’s discretion
• PRIOR TO CELL PRODUCT ADMINISTRATION: Subject has no evidence of uncontrolled infection or sepsis
• PRIOR TO CELL PRODUCT ADMINISTRATION: Negative serum pregnancy test within 7 days of cell product administration (does not need to be repeated if pre-lymphodepletion pregnancy test is within this window)
• PRIOR TO CELL PRODUCT ADMINISTRATION: Creatinine ≤ 2.5 X ULN (within 72 hours prior to infusion)
• PRIOR TO CELL PRODUCT ADMINISTRATION: Bilirubin ≤ 2 X upper limit of normal (ULN), unless attributed to Gilbert's syndrome (within 72 hours prior to infusion)
• PRIOR TO CELL PRODUCT ADMINISTRATION: Aspartate aminotransferase (AST) ≤ 5 X ULN ( ≤ 7 X ULN if liver metastases present) (within 72 hours prior to infusion)
• PRIOR TO CELL PRODUCT ADMINISTRATION: Alanine aminotransferase (ALT) ≤ 5 X ULN ( ≤ 7 X ULN if liver metastases present) (within 72 hours prior to infusion)
• PRIOR TO CELL PRODUCT ADMINISTRATION: Subject is a good candidate for treatment with iC9-CAR.CSPG4 T cells per the clinical investigator’s discretion.

Exclusion Criteria

• Eligibility single subject exceptions are not permitted for Lineberger Comprehensive Cancer Center investigator initiated trials under any circumstances. Other types of single subject exceptions may be allowed if proper regulatory review has been completed in accordance with Lineberger Comprehensive Cancer Center’s single subject exceptions policy