Autologous CAR-T Cells Targeting B7-H3 in PDAC

Number of participants with adverse event

Number of participants with adverse event (AE)s as a measure of safety and tolerability of intraventricular administration iC9-CAR.B7-H3 T cells in subjects with progressive recurrent or refractory pancreatic cancer. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) are defined as at least possibly related to iC9-CAR.B7-H3 T cell product administration.

Cytokine Release Syndrome

Cytokine Release Syndrome (CRS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild (Symptomatic Management): Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.

Neurotoxicity

Neurotoxicity will be graded according to the Central Nervous System (CNS) Toxicity criteria. Grade 0: Normal or no change from baseline exam at start of therapy, Grade 1: Mild lethargy and/or irritability or visual, motor, or sensory symptoms without change in neurological exam, Grade 2: Moderate lethargy, disorientation, or psychosis lasting \< 48 hours or mild increase in pre-existing neurological deficit, Grade 3: \>48hours of severe lethargy, but responsive to verbal stimuli or disorientation or psychosis lasting \>48 hours, Grade 4: Coma, unresponsive to verbal stimuli, increasing neurological deficit above grade 3, evidence of herniation, development of uncontrolled seizures, intracerebral hemorrhage.

Definition of Dose Limiting Toxicity

The Dose Limiting Toxicity of iC9-CAR.B7-H3 T cells will be determined based on the modified 3+3 dose finding rule defined in the protocol. Dose escalation will be performed considering the dose-limiting toxicities (DLTs), dose level (DL) will be increased unless there is no DLT.

Progression Free Survival (PFS)

PFS is measured from the first day of lymphodepletion chemotherapy to progression as defined per response evaluation criteria in solid tumors (RECIST 1.1) and immune response evaluation criteria in solid tumors ( iRECIST) or death. RECIST1.1: Complete Response, the disappearance of all target lesions; Partial Response, \>=30% decrease in the sum of the longest diameter; Stable Disease, no response or less response than Partial or Progressive; or Progressive Disease, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. irRECIST: Complete Response disappearance of all lesions, no new lesions, lymph nodes \< 10 mm in short axis; Partial Response, ≥30% decrease in the sum of lesions; Stable response, not meeting criteria for irCR, irPR, or irPD; Progressive Disease, ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target.

Overall Survival (OS)

OS will be measured from the first day of lymphodepleting chemotherapy prior to iC9-CAR.B7-H3 T cell infusion to date of death for any cause.

The disease control rate (DCR)

DCR will be defined as the percentage of subjects with \[complete response + partial response + stable disease\] as defined by per response evaluation criteria in solid tumors (RECIST 1.1) and immune response evaluation criteria in solid tumors ( iRECIST) or death. RECIST1.1: Complete Response, the disappearance of all target lesions; Partial Response, \>=30% decrease in the sum of the longest diameter; Stable Disease, no response or less response than Partial or Progressive; or Progressive Disease, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. irRECIST: Complete Response disappearance of all lesions, no new lesions, lymph nodes \< 10 mm in short axis; Partial Response, ≥30% decrease in the sum of lesions; Stable response, not meeting criteria for irCR, irPR, or irPD; Progressive Disease, ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir.