Genetically Engineered Cells (iC9-CAR.B7-H3 T cells) for the Treatment of Patients with Relapsed or Refractory Triple Negative Breast Cancer

Inclusion Criteria

• ELIGIBILITY CRITERIA PRIOR TO PROCUREMENT:
• 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 or legally authorized representative
• Age ≥ 18 years at the time of consent
• Karnofsky score of > 60%
• Histologically confirmed TNBC (estrogen receptor [ER]-, progesterone receptor [PR]-, HER2-negative) * ER- and PR-negative: defined as < 1% staining by immunohistochemistry (IHC) * HER2-negative: defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio < 2.0
• Subjects with stable brain metastases are eligible if were incidentally found and either not felt to require treatment or have been treated (stereotactic radiosurgery [SRS] or resection). Patients with a history of symptomatic central nervous system (CNS) involvement or multiple metastases requiring whole brain radiation are not eligible
• Subject has life expectancy of ≥ 12 weeks
• Subjects must have progressed on at least one line of therapy in the metastatic setting. Subjects that progress within 6 months post (neoadjuvant) polychemotherapy with immune checkpoint inhibitor (ICI), could be eligible for enrollment after confirmation with the principal investigator
• Subject must have no active infection with HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) (tests can be pending at the time of cell procurement; only those subjects meeting the above criteria will have cells manufactured * 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 who use systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent will be excluded from procurement; 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
• 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 and after CAR T cell infusion if 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 and or evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Hemoglobin (Hgb) ≥ 8 g/dL (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. 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
• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (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. 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
• Platelets ≥ 75 × 10^9/L (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. 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
• Creatinine clearance ≤ 2 × upper limit of normal (ULN) (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. 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
• Bilirubin ≤ 1.5 × 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 × ULN (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. 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
• Aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN if liver metastases present) (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. 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
• Alanine aminotransferase (ALT) ≤ 3 × ULN (≤ 5 × ULN if liver metastases present) (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. 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
• Pulse oximetry ≥ 90 % on room air (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. 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
• ELIGIBILITY CRITERIA PRIOR TO LYMPHODEPLETION:
• Subject must have progressed on at least 1 prior lines of therapy in the metastatic setting. Subjects that progress within 6 months post (neoadjuvant) polychemotherapy with ICI, could be eligible for enrollment after confirmation with the principal investigator
• Subject has not received any investigational agents or any tumor vaccines within 3 weeks prior to lymphodepletion.
• Subject has not received chemotherapy or radiation therapy within the previous 3 weeks prior to lymphodepletion
• Subjects who use systemic corticosteroids at doses ≥ 10 mg prednisone daily or its equivalent are not eligible for lymphodepletion; 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
• Imaging results from within 10 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-CAR.B7-H3 T cells that meet the Certificate of Analysis acceptance criteria
• Hemoglobin (Hgb) ≥ 8 g/dL (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. 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
• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (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. 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
• Platelets ≥ 75 × 10^9/L (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. 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
• Creatinine clearance ≤ 2 × ULN (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. 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
• Bilirubin ≤ 1.5 × 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 × ULN (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. 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
• Aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN if liver metastases present) (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. 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
• Alanine aminotransferase (ALT) ≤ 3 × ULN (≤ 5 × ULN if liver metastases present) (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. 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 clearance ≤ 2.5 × ULN (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
• Bilirubin ≤ 2 × ULN, unless attributed to Gilbert’s Syndrome (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
• Aspartate aminotransferase (AST) ≤ 5 × ULN (≤ 7 × ULN if liver metastases present) (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
• Alanine aminotransferase (ALT) ≤ 5 × ULN (≤ 7 × ULN if live metastases present) (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-CAR.B7-H3 T cells per the clinical investigator’s discretion
• 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