Global multi-center phase I trial of the intraperitoneal infusion of anti-EpCAM x anti-CD3 bispecific antibody catumaxomab for advanced gastric carcinoma with peritoneal metastasis.

e16102 Background: Advanced gastric cancer (GC) patients (pts) have high incidence of peritoneal metastasis (PM), resulting in ascites, cachexia and poor life quality. EpCAM is highly expressed on GC but no on peritoneum. Catumaxomab intraperitoneal infusion (i.p.) was previously demonstrated to eradicate EpCAM+ cancers and control the malignant ascites in Europe (Heiss. Int. J. Cancer.2010). We present initial safety, pharmacokinetics (PK), and efficacy from the multi-center phase I trial of Catumaxomab on GC pts with PM in Asian population (NCT04222114). Methods: GC pts who had progressed on at least two prior standard systemic therapies with peritoneal metastasis were enrolled. Pts received Catumaxomab i.p. of 10 μg, 20 μg, 50 μg and 150 μg on days 1, 4, 8 and 11, respectively in the 1st cycle. From the 2nd cycle, Pts received Catumaxomab i.p. of 20 μg, 50 μg, 150 μg on days 1, 4 and 8, respectively. The cycle was 42 days in Cohort A, and 28 days in Cohort B. Catumaxomab PK were evaluated, tumor measurements and quantification of ascites by five-point method (Oriuchi, JJCO,2005) were performed Q6W. The primary endpoint was overall survival (OS); secondary endpoints were response rate of ascites, progression-free interval of peritoneal metastatic lesions and puncture-free survival (PuFS); Data cut-off date was Jan 29,2022. Results: 17 pts from 14 sites (median age: 52.5 yr, ECOG PS: 0 [n=2], 1 [n=14], 2[n=1], Cohort A:9, Cohort B:8) were treated. There were no dose-limiting toxicities (DLTs). The most common treatment-emergent adverse event (TEAE) was pyrexia (76.5%) and abdominal pain (58.8%). Grade ≥3 treatment related adverse events (TRAE) of abdominal pain (23.5%), bilirubin conjugated increased (23.5%), lymphocyte count decreased (17.6%), ALT increased (11.8%), and AST increased (11.8%) were reported. No treatment related death or neurotoxicity occurred in the study. Median overall survival was 102 days (95%CI: 38-166), with 10 (58.8%) deaths observed. For ascites, CR+PR was observed in 4 cases (33%), no PD case was reported. No therapeutic ascites drainage was recorded after cycle 1. Median PuFS was 116 days (95%CI: 28-157). Median progression-free interval of peritoneal metastatic lesions was 102 days (95%CI: 38-166). PK: Catumaxomab concentrations in plasma increased in a dose-dependent manner and were similar to Caucasian population in Europe. Conclusions: This clinical study indicated that multiple cycles of Catumaxomab i.p. were safe and well tolerated in Asian population. PK profile was similar. Early efficacy signals were promising, especially in pts with ascites, which will be further investigated in phase 3 study. Clinical trial information: NCT04222114.