132P - A phase I clinical trial of QLS31905 in advanced solid tumors

Background

QLS31905 is a novel Claudin18.2/CD3 bi-specific antibody. This study aimed to evaluate its safety, tolerability, and antitumor activity in advanced solid tumors.

Methods

This phase I trial (NCT05278832) recruited pts with advanced solid tumors who failed standard treatment, or were inapplicable to or had no standard treatment. The dose-escalation stage, adopting accelerated titration and interval 3+3 design, recruited pts regardless of Claudin 18.2 (CLDN18.2) expression. QLS31905 was administered in nine sequential single doses (0.5, 1.5, 5, 15, 45, 100, 200, 350, and 500 μg/kg qw or q2w) with/without priming dose. The dose-expansion stage recruited CLDN18.2-positive pts (expression ≥1% of tumor cells). The primary endpoint was dose limiting toxicities (DLT) and maximum tolerated dose (MTD) in dose-escalation stage, and was objective response rate (ORR) in dose-expansion stage.

Results

As of July 17, 2023, 52 pts were included. In dose-escalation stage, 22 pts were included from 0.5 to 350 μg/kg qw, and 500 μg/kg q2w cohort is ongoing. Two dose-expansion cohorts, 200 μg/kg qw or 350 μg/kg q2w, included 30 pts. Of 52 pts, 31 had gastric or gastro-esophageal junction cancer and 12 had pancreatic cancer (PC). DLT did not occur. MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 51 pts (98.08%), of which 21 (40.38%) were ≥grade 3. Treatment-related serious adverse events (AEs) occurred in 10 (19.23%) pts. Two pts (3.85%) discontinued treatment due to AEs. The most common TRAE was fever (30, 57.69%), nausea (26, 50.00%), and decreased white blood cell count (18, 34.62%). Two pts had ≥grade 3 cytokine release syndrome, both in the 350 μg/kg qw cohort. Among pts in 200 μg/kg qw cohorts or above dose levels, ORR was 11.1% (3/27) and disease control rate (DCR) was 63.0% (17/27). Three pts with partial responses (2 in PC and 1 in gallbladder cancer) showed intermediate (≥40% of tumor cells) or high (≥70% of tumor cells) CLDN18.2 expression. Of 14 pts with SD (9 in gastric cancer, 4 in PC, and 1 in duodenal cancer), eight had target lesion reduction, among whom seven showed intermediate or high CLDN18.2 expression.

Conclusions

QLS31905 showed safety, tolerability, and preliminary antitumor activity in advanced solid tumors.

Clinical trial identification

NCT05278832.

Legal entity responsible for the study

Qilu Pharmaceutical Co., Ltd.

Funding

Qilu Pharmaceutical Co., Ltd.

Disclosure

Y. Li, L.Gu, L.Li, X.Kang: Other, Personal, Full or part-time Employment: Qilu Pharmaceutical. All other authors have declared no conflicts of interest.