18P - Adoptive cell therapy (ACT) with bispecific gamma delta TCR+ invariant TCR+ NKT-like cells for multiple myeloma (MM): Comparison of preconditioning (PC) on outcome

Background

AVM0703 (AVM) is the subject of an actively enrolling US trial in relapsed/refractory (R/R) no-option Non-Hodgkin’s Lymphoma (NHL), with drug related adverse events limited to grades 1-3 and durable complete (CR) and partial responses (PR) to date. Acute supra-pharmacologic doses (>6 mg/kg) of AVM0703 mobilized endogenous bispecific gdTCR+ invTCR+ Natural Killer T-like cells (AVM_NKT) (PCT/US21/19773) in mice, humanized mice and clinical trial patients1. An ACT model was conducted to verify the direct tumor killing activity of AVM0703 induced novel immune cells (AVM_NKT) and to determine the effect of different PC on tumor killing of the ACT.

Methods

MOPC315 (Balb/c) MM cells were inoculated into the flank as single cell suspensions. When tumor volume reached ∼400mm³ well-established tumors, mice were PC’d with human equivalent dose (HED) cyclophosphamide-fludarabine (CyFlu HED 500/30 mg/mm²), with Placebo (PL) or with AVM0703 HED 18 mg/kg. ACT splenocytes (3.3M) from mice dosed with PL or AVM were iv injected 48 hours later (PL_ACT had 8,240 AVM_NKT and AVM_ACT had 150,000). The next day (13-16 hours later) the mice were euthanized and remaining live MOPC cells were measured in the tumor, spleen, bone marrow, thymus and blood by flow cytometry.

Results

PC was necessary for AVM_ACT effect since there was no difference in live MOPC cells between AVM_ACT versus PL_ACT in mice PC’d with PL. AVM PC was equivalent to CyFlu PC against MOPC in tumor and spleen when AVM_ACT were transferred. Neither AVM nor CyFlu PC (with AVM_ACT) reduced MOPC in blood, bone marrow or thymus compared to PL PC. Repeat daily AVM and CyFlu dosing for PC will be explored in subsequent studies. Table: 18P

Conclusions

AVM0703 could be a less-toxic PC agent before CarT or other ACT. 1 Blood 2021:138(S1) 4557

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

AVM Biotechnology, LLC.

Funding

AVM Biotechnology, LLC.

Disclosure

T.A. Deisher: Financial Interests, Personal, Officer, I am the Founder, CSO and a Board member of AVM Biotechnology, LLC: AVM Biotechnology, LLC; Financial Interests, Personal, Ownership Interest, I am the Founder of AVM Biotechnology, LLC and own 41% of the units: AVM Biotechnology, LLC. S.H. Sawas: Financial Interests, Institutional, Full or part-time Employment, Full-Time Employee at AVM Biotechnology since August 2020: AVM Biotechnology; Financial Interests, Personal, Ownership Interest, PIU Shares in the currently private company: AVM Biotechnology. All other authors have declared no conflicts of interest.