Abstract 539P
Background
Malignant ascites in patients (pts) who had failed standard therapy have no effective and durable treatment. M701 is an anti-EpCAM/CD3 bispecific antibody which can engage the T cells and eliminate the EpCAM positive tumor cells. Here we report the interim results of a phase I trial of M701 in pts with malignant ascites who had failed standard therapies.
Methods
M701 was initially evaluated in a 2-5-10-25μg dose-escalating cohort, then 50, 100, 200, 300 and 400μg cohorts. Doses were administered by i.p infusion QW, DLT and efficacy was evaluated 1 wk after 4 doses. Continuous administration was allowed until ascites recurrence or intolerance. Primary objectives included safety and tolerability. Secondary objectives included PK/PD, immunogenicity and efficacy. The drained ascites volume and the CT images before each dosing were used to evaluate the efficacy according to the WHO criteria. The EpCAM+/CD45+ cells ratio in the ascites was used as a biomarker.
Results
As of Feb 2021, 23 pts had been enrolled (median age 50 years, 26.1% male, median of 4 lines of prior systemic therapy, ovarian cancer, n=12; gastric cancer, n=5; other cancers, n=6). 16 pts finished the DLT evaluation (median dosing 4.5，range 4-15). 7 pts dropped out due to tumor complications, AE or other reasons. The DLT dose had not been reached yet. The AEs were listed below: Table: 539P
| Any grade | ≥3 grade | |
| Any TRAE | 82.6% (19/23) | 21.7% （5/23） |
| Most frequent TRAE | Hypoproteinemia 34.8% Anemia 26.1% Hypokalemia 17.4% Hyponatremia 17.4% | Anemia 8.7% Hypokalemia 4.3% Hyperglycemia 4.3% |
For those 16 pts, the ascites ORR was 62.5% (10/16), DCR was 100% (16/16), including 3 CR, 7 PR and 6 SD cases. The median OS was 152 days (range 43-516). The median OS was 148 days and 209 days in ovarian and gastric cancer pts, respectively. The EPCAM+/CD45+ cells ratio was keeping decreasing in those PR and CR pts that indicated the T cell continuous recruiting and tumor cells elimination.
Conclusions
I.p. infusion with M701 prevented the accumulation of ascites. OS showed an improved trend in pts with gastric and ovarian cancer. These interim data support further development of M701 for pts with malignant ascites.
Clinical trial identification
NCT04501744.
Editorial acknowledgement
Legal entity responsible for the study
Wuhan YZY Biopharma Co., Ltd.
Funding
Wuhan YZY Biopharma Co., Ltd.
Disclosure
J. Xu: Non-Financial Interests, Principal Investigator: Wuhan YZY Biopharma Co., Ltd. S. Huang: Financial Interests, Institutional, Full or part-time Employment: Wuhan YZY Biopharma Co., Ltd. M. Pei: Financial Interests, Full or part-time Employment: Wuhan YZY Biopharma Co., Ltd. X. Wang: Financial Interests, Institutional, Full or part-time Employment: Wuhan YZY Biopharma Co., Ltd. P. Zhou: Financial Interests, Institutional, Full or part-time Employment: Wuhan YZY Biopharma Co., Ltd. All other authors have declared no conflicts of interest.