Clinical Trials

Inclusion Criteria:

• ≥18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (ECOG status of 2 will be permitted for subjects with AML)
• Minimum life expectancy of 12 weeks
• Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document
• Diagnosed with r/r TCL, BCL, or AML
• For lymphoma subjects, measurable disease must be present per imaging (positron emission tomography [PET]–computed tomography [CT] or CT) according to Lugano criteria. Note: Previously irradiated lesions will be considered measurable only if progression of the irradiated lesion is documented following completion of radiation therapy. For TCL, measurable disease may alternatively be present per the Modified SeverityWeighted Assessment Tool (mSWAT) or peripheral blood tumor burden B2 classification.
• For subjects with BCL: CD70 positivity (≥10% of cells) by immunohistochemistry (IHC) in tissue collected by excisional or core biopsy of a representative tumor lesion as determined by laboratories meeting applicable local requirements (e.g., Clinical Laboratory Improvement Amendments or equivalent for non-US locations). Flow cytometry performed on BM aspirate may also be acceptable.
• Provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (if the investigator deems it safe and clinically feasible), or BM aspirate containing leukemic blasts; a sample collected within 3 months prior to enrollment and after the last systemic or targeted therapy postprogression is acceptable.
• Meets protocol-specified criteria to undergo LD chemotherapy and CAR T cell infusion.
• Adequate organ function as below:
  • Renal: Estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m2
  • Liver:
    •  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × upper limit of normal (ULN)
    • Total bilirubin <2 × ULN (for Gilbert’s syndrome or lymphomatous infiltration of the liver: total bilirubin <3 mg/dL)
  • Cardiac: Hemodynamically stable and left ventricular ejection fraction (LVEF) ≥45% by echocardiogram or ≥50% by multigated acquisition scan
  • Pulmonary: Oxygen saturation level on room air >91%, per pulse oximetry
  • Hematologic:
    • Platelet count >25,000 and absolute neutrophil count (ANC) > 500/mm3 (AML subjects exempt)
    • Additional requirement for AML subjects: White blood cell <25 × 109 /L (hydroxyurea is permitted to meet this requirement)
• Subjects of childbearing potential (postmenarcheal, has an intact uterus and at least 1 ovary, and is less than 1 year postmenopausal) must agree to use an acceptable, highly effective method of contraception (as specified in the protocol) from enrollment through at least 12 months after last CTX131 infusion.
• Subjects capable of producing sperm who are or may become sexually active with partners of childbearing potential must agree to use acceptable, effective method(s) of contraception (as specified in the protocol) from enrollment through at least 12 months after last CTX131 infusion.

Exclusion Criteria:

• Prior treatment with anti-CD70 targeting agents
• Known contraindication to any LD chemotherapy agent(s), any of the excipients of CTX131 product, (or azacitidine for select Phase 2 cohorts)
• Active CNS manifestation of underlying disease in screening assessment, i.e., brain magnetic resonance imaging (MRI); flow cytometry and/or cytology of cerebrospinal fluid (CSF) may also be performed
• History or presence of clinically relevant CNS pathology such as seizure, stroke, severe brain injury, cerebellar disease, myelopathy (e.g., tropical spastic paraparesis), history of posterior reversible encephalopathy syndrome with prior therapy, or another condition that in opinion of investigator may increase CAR T-related toxicities
• Grade ≥3 pericardial effusion at the time of enrollment. History of pericardial effusion, regardless of grade, should be discussed with the medical monitor.
• Unstable angina, arrhythmia, or myocardial infarction within 6 months prior to screening
• Uncontrolled bacterial, viral, or fungal infection based on investigator judgment in consultation with the medical monitor
• Positive for human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), or active hepatitis B virus or hepatitis C virus infection. Subjects with prior history of hepatitis B or C infection who have documented undetectable viral load (by quantitative polymerase chain reaction [qPCR] or nucleic acid testing) are permitted.
• Diagnosis with another invasive malignancy in the last 5 years with the exception of nonmelanoma skin cancer and malignancies deemed by the investigator and medical monitor to be of low likelihood for recurrence
• Clinical signs of HLH: A combination of fever, bicytopenia, hypertriglyceridemia or hypofibrinogenemia, and ferritin >500 µg/mL
• For AML cohorts: diagnosed with acute promyelocytic leukemia, BCR-ABL positive leukemia, AML secondary to prior therapy or history of genetic syndrome associated with BM failure
• Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy
• Prior solid organ or allogeneic BM transplantation, except for AML cohorts if at least 3 months since allogeneic HSCT, not receiving immunosuppressive therapy or donor lymphocyte infusion post SCT in the 2 weeks prior to lymphodepletion, and have no clinically active GvHD
• Concurrent systemic treatment with an anticancer biologic (e.g., monoclonal antibody) within 30 days prior to CTX131 infusion or with a non-biological anticancer drug within 14 days prior to CTX131 infusion. Mogamulizumab treatment is prohibited 50 days prior to CTX131 infusion. For r/r AML, hydroxyurea is considered an exception.
• Treatment with CD19-targeting CAR-T within 6 months prior to CTX131 infusion
• Use of radiotherapy within 7 days prior to LD chemotherapy
• Requiring >10 mg/day of prednisone or equivalent doses of other corticosteroids or other immunosuppressive drugs within 14 days of CTX131 infusion. Use of physiological doses of steroids (e.g., ≤10 mg/day prednisone or equivalent) will be permitted for subjects previously on steroids if clinically indicated.
• Diagnosis of significant psychiatric disorder that could seriously impede the subject’s ability to participate in the study
• Received live, replication-competent vaccines or herbal medicines as part of traditional Chinese medicine or non-over-the-counter herbal remedies within 28 days prior to enrollment

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/242024. Questions regarding updates should be directed to the study team contact.