Genetically Modified Immune Cells (iC9-GD2.CAR.IL-15 T Cells) for the Treatment of Extensive Stage Small Cell Lung Cancer or Stage IV Non-small Cell Lung Cancer

Inclusion Criteria

• INCLUSION CRITERIA FOR STUDY:
• 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 extensive stage small cell lung cancer or stage IV NSCLC as defined by the American Joint Committee on Cancer (AJCC) * Subjects with extensive stage (ES)-SCLC must have been previously treated with a platinum doublet (typically Carboplatin plus Etoposide) and a PD1 or PDL1 (PDx) inhibitory agent * Subjects with stage IV NSCLC must have been previously treated with a platinum doublet and a PDx inhibitory agent. Subjects with a biologic predictor of low probability of PDx response are exempt from the PDx requirement * Subjects with non-squamous NSCLC must have had molecular testing. In the case of an actionable molecular change with a Food and Drug Administration (FDA)-approved therapeutic, the subject must have been previously treated with targeted therapy
• 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
• 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 has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Subjects with stable or improving central nervous system (CNS) metastasis as adjudicated by radiographic or clinical evidence are eligible for therapy. Similarly, patients with stable leptomeningeal metastases will be considered eligible for treatment if stability is verified by the medical monitor
• ELIGIBILITY CRITERIA TO BE MET PRIOR TO PROCUREMENT:
• Written informed consent to undergo cell procurement explained to, understood by, and signed by the subject
• Subject has life expectancy of >= 12 weeks
• Subject must be platinum refractory and either currently receiving or has previously received a PD1/PDL1 inhibitor
• Subject must not have an active infection with HIV, HBV, HCV (tests can be pending at the time of cell procurement; only subjects meeting the criteria as described will be infused). 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.
• Subjects must not be using 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
• 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
• Hemoglobin (Hgb) >= 8 g/dL at least 1 week following last transfusion (obtained within 7 days of cell procurement)
• Absolute Neutrophil Count (ANC) >= 1.0 x 10^9/L (obtained within 7 days of cell procurement)
• Platelets >= 100 x 10^9/L (obtained within 7 days of cell procurement)
• Creatinine =< 2 x upper limit of normal (ULN) (obtained within 7 days of cell procurement)
• Bilirubin =< 1.5 x 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 (obtained within 7 days of cell procurement)
• Aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x ULN if liver metastases present) (obtained within 7 days of cell procurement)
• Alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x ULN if liver metastases present) (obtained within 7 days of cell procurement)
• Pulse oximetry >= 90 % on room air (obtained within 7 days of cell procurement)
• Note: Hematology and other lab parameters that are ≥ grade 2, but still meet criteria for study entry are allowed. Prior administration of myeloid growth factor or transfusion must occur at least 2 weeks prior to procurement. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for change in severity after cell infusion and/or worsen from baseline during therapy.
• No known myocardial infarction within the last 6 months prior to infusion or uncontrolled cardiac disease. No Class 3 or higher New York Heart Association (NYHA) Congestive Heart Failure. In the absence of symptoms echocardiograph (ECHO) is not required for eligibility
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION:
• Written informed consent to undergo therapy with iC9-GD2.CAR.IL-15 T-cells explained to, understood by and signed by the subject; subject given a copy of informed consent form
• Subject must be platinum refractory and PD1 exposed
• No major surgery within 28 days to lymphodepletion
• Subject has not received any investigational agents or any tumor vaccines within 6 weeks prior to lymphodepletion
• Subject has not received chemotherapy or radiation therapy within the previous 3 weeks prior to lymphodepletion
• Subjects must not be using 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
• Subject is not currently receiving a prohibited medication that should not be concurrently received with cyclophosphamide
• Must have 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)
• Subject must have available iC9-GD2.CAR.IL-15 T-cells that meet the Certificate of Analysis acceptance criteria
• Hgb >= 8 g/dL acceptable to reach via transfusion (obtained within 72 hours prior to lymphodepletion)
• ANC >= 1.0 x 10^9/L (obtained within 72 hours prior to lymphodepletion)
• Platelets >= 100 x 10^9/L (obtained within 72 hours prior to lymphodepletion)
• Creatinine =< 2 x ULN (obtained within 72 hours prior to lymphodepletion)
• Bilirubin =< 1.5 x ULN. Subjects with Gilbert’s syndrome may be enrolled despite a total bilirubin level > 1.5 mg/dL if their conjugated bilirubin is < 1.5 × ULN (obtained within 72 hours prior to lymphodepletion)
• AST =< 3 x ULN (=< 5 x ULN if liver metastases present) (obtained within 72 hours prior to lymphodepletion)
• ALT =< 3 x ULN (=< 5 x ULN if liver metastases present) (obtained within 72 hours prior to lymphodepletion)
• Note: Hematology and other lab parameters that are ≥ grade 2, but still meet criteria for study entry are allowed. Prior administration of myeloid growth facture or transfusion is permitted Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for change in severity after cell infusion and/or worsen from baseline during therapy
• 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
• Subject does not have rapidly progressive disease, per treating oncologist’s discretion
• Subject is a good candidate for CAR T cell therapy, per treating oncologist’s discretion
• ELIGIBILITY CRITERIA PRIOR TO CELL PRODUCT ADMINISTRATION:
• Subject has no evidence of uncontrolled infection or sepsis
• 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)
• Creatinine =< 2.5 x ULN (obtained within 72 hours prior to infusion)
• Bilirubin =< 2 x ULN, unless attributed to Gilbert’s Syndrome (obtained within 72 hours prior to infusion)
• AST =< 5 x ULN (=< 7 x ULN if liver metastases present) (obtained within 72 hours prior to infusion)
• ALT =< 5 x ULN (=< 7 x ULN if liver metastases present) (obtained within 72 hours prior to infusion)
• Note: Hematology and other lab parameters that are ≥ grade 2, but still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for change in severity after cell infusion and/or worsen from baseline during therapy.
• Subject is a good candidate for treatment with iC9-GD2.CAR.IL-16 T-cells per the clinical investigator’s discretion
• For subjects on dose level 3 receiving a split dose: In order to receive the second half dose, the following conditions must be met: No ICANS (of any grade), no > grade 1 CRS, and no uncontrolled infection, per principal investigator adjudication. Subjects who meet these conditions within 14 days of the first dose may receive the second part of the dose. Otherwise, they will only receive the first half dose