Second-line ASKB589 plus chemotherapy for advanced gastric or gastroesophageal cancers: Results from cohort 5 of a phase I/II study.

4044 Background: ASKB589 is a humanized monoclonal antibody with enhanced affinity for CLDN18.2 and increased ADCC activity. It has shown favorable safety profiles and promising antitumor effects in phase I/II clinical study (NCT04632108) involving first-line patient(pt)s with advanced gastric or gastroesophageal（G/GEJ） cancers. Here, we present the findings from cohort 5 that ASKB589 in combination with chemotherapy as second-line treatment for patients with advanced G/GEJ cancers. Methods: Cohort 5 from NCT04632108 is designed to evaluate the safety and preliminary efficacy of ASKB589 (at 2 doses: 6mg/kg or 10mg/kg Q3W) plus chemotherapy as second line treatment in pts with G/GEJ cancers. Eligible pts who had confirmed progressive disease during treatment with first line standard of therapy were enrolled. CLDN18.2 statuses were analyzed retrospectively using IHC DS-3 LDT assay. Primary endpoint was safety. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression free survival (PFS) assessed by investigator per RECIST v1.1 and overall Survival (OS). Results: As of December 20, 2024, 47 pts were enrolled in the 2L cohort and received 6mg/kg ASKB589 plus chemotherapy. Among them, 44 pts were treated with 6mg/kg ASKB589 plus paclitaxel, while 2 pts received 6mg/kg ASKB589 plus docetaxel, and 1 pt received 6mg/kg ASKB589 plus irinotecan. 17 (27%) pts had received immunotherapy previously.The confirmed ORR was 34.2% in 38 measurable and evaluable CLDN18.2 moderate to high GC/GEJ pts (CLDN18.2 moderate to high was defined as ≥40% of tumor cells with ≥2+ intensity by immunohistochemistry). 14 pts (36.8%) had stable disease, and the DCR was 71.1%. For the ASKB589 plus paclitaxel subgroup (n = 35, with evaluable response), the confirmed ORR was 31.1%, DCR was 71.4%. In the intention-to-treat analysis, the median PFS with 6mg/kg ASKB589 plus chemotherapy was 5.26 months (95%CI: 2.66, 7.06), and the median OS was 11.14 months (95%CI: 8.80, 18.20). In the ASKB589 plus paclitaxel subgroup, the median PFS was 4.63 months (95%CI: 2.04, 7.06) and median OS of 13.73 months (95%CI: 8.80, 18.20) respectively. Treatment related adverse events (TRAEs) occurred in all pts including 26 (55.3%) pts with grade ≥3 TRAEs. The most common grade ≥3 TRAEs (≥5%) were neutrophil count decreased (42.6%), white blood cell count decreased (17%), lymphocyte count decreased (8.5%), and hypoalbuminemia (8.5%). Conclusions: The results of cohort 5 from NCT04632108 have shown that ASKB589 plus chemotherapy, as 2L treatment in pts with advanced GC/GEJ cancers have promising antitumor activity and response durability, especially in the ASKB589 plus paclitaxel subgroups. Both treatment regimens are well tolerated. Further development of ASKB589 combination therapy for CLDN18.2-positive GC/GEJ pts 2nd line treatment is planned. Clinical trial information: NCT04632108 .