A phase I/II study of ASKB589 (anti-claudin 18.2 [CLDN18.2] monoclonal antibody) in patients with solid tumors.

397 Background: ASKB589 is a humanized IgG1 monoclonal antibody against Claudin 18.2 (CLDN18.2) with high affinity and enhanced antibody-dependent cellular cytotoxicity activity. We report preliminary safety and efficacy data from an ongoing Phase I/II, first-in-human, dose-escalation and expansion study of ASKB589 in patients (pts) with advanced solid tumors (NCT04632108). Methods: A two-part study was initiated to determine the maximum tolerated dose (MTD), safety and tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ASKB589 as monotherapy (Part A) and in combination with chemotherapy (Part B). Each part used a modified 3 + 3 dose escalation design. Responses were assessed per RECIST 1.1 every 2 cycles (6 weeks). Adverse events (AEs) were graded using CTCAE v5.0. In Part A, pts with heavily pre-treated solid tumors received ASKB589 intravenously (IV) at doses of 0.3, 1, 3, 6, 10,15 or 20mg/kg every 3 weeks (Q3W). In Part B, pts with gastric/gastro-esophageal junction (G/GEJ) cancers received ASKB589 IV at doses of 3, 6, 10 or 15 mg/kg Q3W in combination with capecitabine plus oxaliplatin. Results: As of September 9, 2022, 51 pts received ASKB589 and no drug limiting toxicity (DLT) was observed. In expansion, pts have been enrolled into 6, 10, 15 mg/kg doses. In Part A, 17 pts were enrolled in escalation and 13 in expansion. All pts had metastatic disease, and most (90%) had ≥2 lines of prior therapy. 24 (80%) pts had treatment-related adverse events (TRAEs), the most common being nausea (53%), vomiting (43%), hypoalbuminemia (40%) and loss of appetite (30%). While the majority of TRAEs were grade 1 or 2, 3 pts (10%) had grade 3 events. For the 9 evaluable pts (G/GEJ cancer who received ≥10 mg/kg ASKB589 with at least one post-baseline tumor assessment), 5 pts (45%) had decreases in tumor size (range 1-38% from baseline). 2 pts achieved a partial response (PR) for an objective response rate (ORR) of 22%. In addition, 6 pts had stable disease (SD) for a disease control rate (DCR) of 89%. In Part B, 13 pts were enrolled in escalation and 8 in expansion. These pts were with advanced disease (95% stage IV) and had no prior systemic treatment in this setting. 17 (81%) pts had TRAEs, the most common being nausea (76%), vomiting (66%), hypoalbuminemia (52%), granulocytopenia (38%) and hypoleukemia (33%). While the majority of TRAEs were grade 1 or 2, 8 pts (38%) had grade 3 events. For the 12 evaluable pts (G/GEJ cancer who received ≥6 mg/kg ASKB589 with at least one post-baseline tumor assessment), all had decreases in tumor size (range 6-66% from baseline). 9 pts achieved PR for an ORR of 75%. In addition, 3 pts had SD for a DCR of 100%. The PK profile showed dose-related increases in drug exposure across study doses. Conclusions: ASKB589 showed a manageable safety profile up to doses of 20 mg/kg and promising antitumor activity, both as monotherapy and in combination with chemotherapy. Clinical trial information: NCT04632108 .