Autologous CAR-T Cells Targeting CSPG4 in Relapsed/Refractory HNSCC

Toxicity will be graded as the Number of participants with adverse events (AE)s

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) is defined as at least possibly related to CAR.B7-H3T cell product administration.

CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: 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: 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

Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria.

Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).

An event will be considered a Dose limiting toxicity per NCI CTCAE version 5.0, the CRS Grading and ICANS grading criteria.

• Grade 3-5 allergic reactions related to the CAR-T cell infusion.
• A treatment-emergent Grade 3 CRS that does not improve to Grade 0-1 by 72 hours or Grade 4 CRS
• Grade ≥3 ICANS that is unresponsive to the standard of care interventions and does not decrease to Grade ≤1 within 7 days or grade 4 ICANS of any duration that has evidence of cerebral edema and/or generalized convulsive status epilepticus.
• Any treatment-emergent Grade 4 non-hematologic AE that does not resolve to Grade 2 within 7 days.
• Any Grade 5 events are not due to the underlying malignancy.

The recommended phase 2 dose (RP2D) for administration of iC9-CAR.CSPG4 T cells will be determined based on the modified 3+3 dose finding rule and the tolerability of iC9-CAR.CSPG4 T cells. tolerability of iC9-CAR.CSPG4 T cells will be assessed by NCI-CTCAE v5, ASTCT Consensus ICANS Grading, and CRS Grading Criteria.

The objective response rate will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).

RECIST v1.1: Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.

irRECIST: Complete Response (irCR), Disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis; Partial Response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir.

PFS will be measured from the first day of lymphodepletion chemotherapy prior to iC9- CAR.CSPG4 T cell infusion to progression per RECIST 1.1 or death.

OS will be measured from the first day of lymphodepleting chemotherapy prior to iC9-CAR.CSPG4 T cell infusion to date of death for any cause.

DOR is defined as the time from partial response (PR) or better to progressive disease (PD) per RECIST 1.1. and irRECIST.

Feasibility will be determined by measuring the percent of subjects procured that proceed with lymphodepletion followed by iC9-CAR.CSPG4 T cell infusion.