Pressurized intra-peritoneal aerosol as a delivery system for macrophage reprogramming cellular therapy in conjunction with chemotherapy for the treatment of advanced peritoneal malignancies.

e14537 Background: Novel intraperitoneal delivery systems like Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC) increase the therapeutic access with encouraging responses in patients with peritoneal carcinomatosis unresponsive to systemic therapy. However, survival rates remain at 11-16 months, and treatment options are limited, especially in patients with high tumor burden. Allocetra, an innovative immunomodulatory cellular therapy, has demonstrated antitumor activity in preclinical peritoneal tumor models, reprogramming macrophage function in the tumor microenvironment. The clinical study assesses the applicability and safety of Allocetra given by pressurized intra-peritoneal aerosol, in conjunction with PIPAC. Methods: Allocetra is manufactured from mononuclear cells collected from healthy non-matched donors, and induced to undergo early apoptosis. Safety of administration via pressurized aerosol was assessed by cell recovery and function. The clinical study is a dose-finding safety study with inter- and intra-patient dose escalation of Allocetra to determine safety of intraperitoneal Allocetra administration via pressurized aerosol system (Capnopen, Capnomed, Germany), with PIPAC. Patients have advanced peritoneal cancer, non-eligible for Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Two cohorts (n=3) are treated with escalating doses of Allocetra at 6-week intervals. Two subsequent cohorts (n=3) include patients treated at the maximal tolerated dose, to evaluate the sequencing of Allocetra and PIPAC. Results: Allocetra pressurized aerosol delivery demonstrated stable and acceptable cellular profiles, recovery and potency. In the first clinical cohort (n=3), patients received escalating doses of 1 x 10 9 , 2.5 x 10 9 and 5 x 10 9 Allocetra cells, followed by PIPAC. Patients’ primary diseases were advanced colon and appendicular carcinomas with multiple prior treatment cycles (chemotherapy, biologics and immunotherapy). Patients were followed for a median 15 weeks (range 7-32) for adverse events. Adverse event profile following combined treatment with Allocetra included mostly mild common post surgical events: abdominal pain, pain around surgical wound, shoulder pain, abdominal wall hematoma, rash around surgical wound, urinary tract infection, inferior epigastric artery bleeding, and infected hematoma. None were considered related to Allocetra. All the patients are alive and continue to be followed. Conclusions: Initial results from the study indicate a favorable safety profile following pressurized intra-peritoneal aerosol administration of Allocetra cellular therapy. Additional patients will be treated with escalating doses of Allocetra to assess safety and initial response to treatment. Clinical trial information: NCT05431907 .