208MO - Immune related adverse events and biomarkers after Anbal-cel, novel anti-CD19 CAR-T therapy with dual silencing of PD-1 and TIGIT: Updates from phase I study

Background

Anbal-cel is a novel 2^nd generation autologous CD19 CAR-T cell therapy which has been knock-downed for PD-1 and TIGIT using OVIS platform and demonstrated the superior T-cell functionality compared with CD19 CAR-T cells at preclinical studies.

Methods

This Phase 1 dose escalation part was evaluated for the safety and preliminary efficacy in patients with r/r LBCL. Anbal-cel was administered at dose level 1 (2x10⁵ cells/kg), DL2 (7x10⁵ cells/kg) or DL3 (2x10⁶ cells/kg). Blood samples have been collected to assess PK, cytokine levels, immune phenotypes and safety etc.

Results

As of May 25 2022, 11 patients with r/r DLBCL were infused with Anbal-cel; 4pts at DL1, 3pts at DL2 and 4pts at DL3. Median manufacturing time was 8 days (range 5-11) and median CD4:CD8 ratio of final product was 1.1. Median knock-down rate of PD-1 and TIGIT was 65% and 96% respectively. Complete response rate was 82% (9/11) and CAR genes were detectable at 6 months in 4 out 5 evaluable patients by qPCR method. Of 11 patients, 5 (45%) experienced CRS with median onset time of 7 days (range 1-16) and median duration of 5 days (range 1-19) and 2 (18%) experienced grade 3 CRS. One patient dosed at DL3 experienced grade 2 ICANS. Grade ≥3 Anemia, neutropenia and thrombocytopenia at day 28 was observed at 22%, 82%, 55% respectively and incidence of grade ≥3 cytopenia was correlated with the dose of Anbal-cel. The Peak levels of IL-2, 6, 8, 10, TNF-α and MCP-1 were increased proportionally to the dose of Anbal-cel while the peak of IFN-γ ramined indifferent depending on the dose of Anbal-cel. B-cell aplasia was maintained from all responding patients by flow cytometry except for one patient at DL2 whose B-cell was reappeared at 3 months and documented PD at 5 months after achieving CR. LDH and CRP changes were inversely proportional to the dose of Anbal-cel but Ferritin level wasn't found to be related to the dose of Anbal-cel.

Conclusions

Anbal-cel expanded proportionally to the infused dose and cytokines were increased in response to the level of Anbal-cel expanded. Concurrent with the increased Anbal-cel expansion and cytokine levels, prolonged cytopenia was observed in dose responsive manner and these are planned to be further investigated in phase 2.

Clinical trial identification

CRC01-01 (NCT04836507).

Editorial acknowledgement

Legal entity responsible for the study

Curocell Inc.

Funding

Curocell Inc.

Disclosure

J. Kim: Financial Interests, Institutional, Full or part-time Employment: Curocell. All other authors have declared no conflicts of interest.