The first in-human phase 1 clinical trial is being conducted in Japan.
The chimeric antigen receptor (CAR)-expressing natural killer (NK) cell therapy iCAR-ILC-N101 seems to be well-tolerated in 1 patient with ovarian clear cell carcinoma (OCCC) dosed so far in a first in-human phase 1 clinical trial being conducted in Japan.
The trial overview was presented at the American Association for Cancer Research (AACR) Annual Meeting, April 8-13, 2022, by first author Kenichi Harano, MD, National Cancer Center Hospital East Japan.
“...There is theoretically no risk of developing graft-versus host disease because the product does not have a T-cell receptor. The product has a relevant living period in the body, thereby has little concern about residual toxicity and reduces systemic side effects by topical treatment,” Harano and colleagues wrote.
The phase 1 trial is evaluating the safety, toxicity, and efficacy of CAR-ILC-N101 in patients with histologically diagnosed glypican-3 (GPC3)-positive advanced or recurrent OCCC with peritoneal dissemination. Patients must be resistant to standard therapy and have matched HLA-A24 or B52.
One patient was enrolled in July 2021 in the lowest of 3 dose cohorts (0.5x106 cells/kg, 1x106 cells/kg, 3x106 cells/kg) and has been dosed. No dose-limiting toxicities have been observed. The therapy is administered intraperitoneally weekly for 4 weeks. The first patient in each cohort will be observed for 14 days for safety after the first treatment and then receive iCAR-ILC-N101 on days 15 and 22.
The allogeneic iCAR-ILC-N101 therapy is a human leukocyte antigen-homozygous induced pluripotent stem cell-derived, CAR-expressing, GPC3-targeted, innate lymphoid cells/NK cell (ILC/NK) therapy. GPC3 is expressed in hepatoblastoma, hepatocellular carcinoma, and OCCC but not normal tissue. It contains both antigen-specific and NK activating receptor-mediated cytotoxicity and is designed to overcome limitations of autologous CAR T-cell therapies or NK cell therapies.
Intraperitoneal injection of iCAR-ILC-N101 has previously shown efficacy in preclinical studies in GPC3-positive, ovarian tumor-bearing, immunodeficient mouse models. Investigators observed suppressed tumor growth in these models.
“Intraperitoneal administration of iCAR-ILC-N101 is expected to show antitumor activity for OCCC patients with peritoneal dissemination that express GPC3 and reduce systemic side effects, thereby ensuring safety and improving therapeutic efficacy,” Harano and colleagues wrote.