Phase 1 study of AM003, a novel individualized immunotherapy, in a basket of advanced solid tumors.

person Irit Carmi Levy Aummune, Tel Aviv, Israel info_outline Irit Carmi Levy, Leanne Amitzi, Erez Lavi, Neta Zilony - Hanin, Zohar Pode, Raanan Berger, Karen Smith

Authors person Irit Carmi Levy Aummune, Tel Aviv, Israel info_outline Irit Carmi Levy, Leanne Amitzi, Erez Lavi, Neta Zilony - Hanin, Zohar Pode, Raanan Berger, Karen Smith Organizations Aummune, Tel Aviv, Israel, Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel Abstract Disclosures Research Funding No funding sources reported Background: Aummune is developing a unique individualized immunotherapy (‘AM003’), designed to have three activities mediated by three different domains: (1) the ‘Variable Domain, identified de novo for each individual patient, based on its ability to specifically induce cell death on patient’s tumor cells; (2) the ‘General Domain’, designed to engage with immune T cells to cause tumor cell lysis; and (3) a ‘CpG-rich Domain’ that stimulates Antigen Presenting Cells. Aummune’s process begins with sampling the patient’s tumor (via biopsy) and healthy cells (PBMCs). The cancerous cells are grown in a 3D culture and once the cells propagate and reach a critical biomass, they are subjected to Aummune’s proprietary platform for the identification of the Variable Domain. Once a tumoricidal sequence is identified, it is manufactured and the drug product (DP) is assembled at the production facility. Following release, the DP is shipped to the medical site for treatment of the patient. Methods: AM003 is being evaluated as an immune-oncology agent in advanced/metastatic relapsed/refractory solid tumors. A First-In-Human Phase 1, open-label multicenter, dose-escalation study of AM003 is ongoing with the following cohorts: (1) 34mg (2) 68mg and (3) 136 mg of AM003 monotherapy administered intratumorally / local subcutaneously once per week for 4 weeks, followed by 6 doses administered every 2 weeks. Key inclusion criteria include (i) histologically confirmed locally advanced/metastatic solid tumors who received and progressed after, or were intolerant to, at least 1 prior systemic therapy and are not candidates for any therapy known to confer clinical benefit. (ii) lesions that are safely amenable to IT injection. The primary objective is to evaluate the safety and tolerability of AM003. Additional objectives include assessment of preliminary evidence of clinical benefit, pharmacokinetic and pharmacodynamics measurements as well as identification of biomarkers. Endpoints: AEs are assessed according to CTCAE v5, treatment response is determined according to RECIST 1.1 and iRECIST, changes in putative markers are evaluated based on multiple analyses methodologies. 10 patients were included in the dose-escalation part: 1(n=4), 2 (n=3), and 3 (n=3). Cohorts 1, 2 and 3 have been completed without DLTs. The DSMB last reviewed the escalation data in January 2024 and concluded that the trial can continue as planned. Enrollment of 136mg dose expansion is ongoing and completion of the trial will be mid 2024. Clinical trial information: MOH_2022-03-29_010690 .